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yale medicine
The med school’s
largest grant
4
Yale launches stem
cell program
7
Water is life
a letter from niger
24
Making a better
knockout mouse
18
winter 2007
winter 2007
yale medicine
CO N T E N T S
2
4
8
10
12
16
18
24
Water is life
An eph alumna works to bring water to the remote Azawak
region of Niger, where drought is devastating a traditional,
nomadic way of life.
By Ariane Kirtley, m.p.h. ’04
background
Aminata, a Tuareg girl, fetches
water from a marsh.
Photographs by Ariane Kirtley
Little mouse, big science
Geneticist Tian Xu has found a way to make knockout mice
quickly and cheaply. By finding genes and discerning their
functions, he hopes to find cures for gene-related disease.
By Pat McCaffrey
on the cover
Takat and Aminata, Tuareg girls
from Camp Tantigellay Teckniwen,
fetch water from a marsh contaminated with animal and human
waste, and load it into a bag on
a donkey. Water flows only a few
months of the year in the Azawak
plains of Niger in western Africa.
During the dry season inhabitants
spend most days in search of water.
This just in
Chronicle
Rounds
Findings
Books & Ideas
Capsule
30
Fever, internal medicine and Paul Beeson
During his 13 years as chair of internal medicine, Paul Beeson
turned the department into one of the best in the country.
By Richard Rapport, m.d.
36
38
40
46
48
48
49
Faculty
Students
Alumni
In Memoriam
Follow-Up
Archives
End Note
On the Web
yalemedicine.yale.edu
On our website, readers can submit class notes or a change of address,
check the alumni events calendar, arrange for a lifelong Yale e-mail alias
through the virtual Yale Station and search our electronic archive.
2
this just in
New state stem cell
fund awards $7 million
to Yale investigators
how to reach us
Yale Medicine welcomes news
and commentary. Please send
letters (350 words or less) and
news items to Yale Medicine,
300 George Street, Suite 773,
New Haven, CT 06511, or via
e-mail to ymm@yale.edu, and
include a telephone number.
Submissions may be edited for
length, style and content.
yale medicine winter 2007
visit us on the web
As Yale Medicine was in production, Yale scientists received $7
million in grants from the State
of Connecticut Stem Cell Research
Advisory Committee in November
to study aspects of stem cell
biology. The grants were the first
awarded from the $100 million
fund established by the state
last year to promote stem cell
research outside the restrictions
of federal funding. The state
also awarded grants totaling
$12 million to investigators at
the University of Connecticut
and $900,000 to scientists at
Wesleyan University. The total
allocated for 21 research projects
was $19.78 million. A state advisory panel awarded the grants
after reviewing 70 applications.
(See related story, page 7.)
The lion’s share of the Yale
funding went to Michael P.
Snyder, ph.d., professor of
molecular, cellular and developmental biology, to investigate
the neural differentiation of
human embryonic stem cells.
He received $3.8 million.
Haifan Lin, ph.d., director
of the Yale Stem Cell Program,
received $2.5 million to support
a human embryonic stem cell
core facility. The University of
Connecticut received a similar
amount for its core facilities as
well. Diane S. Krause, m.d., ph.d.,
associate professor of laboratory
medicine and pathology and
co-director of Yale’s stem cell
program, received $856,653 to
study a leukemia gene using
human embryonic stem cells.
Yingqun Joan Huang, m.d.,
ph.d., assistant professor
of obstetrics, gynecology and
reproductive sciences, received
$200,000 to study the Fragile
X mental retardation protein in
early human neural development. Eleni A. Markakis, ph.d.,
assistant professor of psychiatry,
received $184,407 to direct the
isolation of neuronal stem cells
from human embryonic stem
cell lines. And Erik Shapiro, ph.d.,
assistant professor of diagnostic
radiology, received $199,975
for using magnetic resonance
imaging to study the directed
migration of endogenous neural
progenitor cells.
“With this first allotment of
money, Connecticut becomes
a national leader in the area of
stem cell research,” said Gov. M.
Jodi Rell in a statement announcing the grants. “We have proven
ourselves able to provide a
place where such research can
be done safely, ethically and
effectively, in addition to providing investment dollars for the
growth of the bioscience industry in Connecticut and making
an investment intended to
improve the health of generations to come.”
Five other states—California,
New Jersey, Maryland, Missouri
and Illinois—have decided to
fund stem cell research.
“After careful consideration
and review by both an international panel of experts and
this committee, we are confident that Connecticut is investing in stem cell research projects
that will yield significant scientific findings in the long term,”
said J. Robert Galvin, m.d.,
m.p.h., chair of the state’s Stem
Cell Research Advisory Committee and Commissioner of
Public Health.
yale medicine
Alumni Bulletin of the
Yale University School of Medicine
Winter 2007, Volume 41, No. 2
Editor in Chief
Michael Kashgarian, m.d. ’58, hs ’63
Professor of Pathology and Molecular,
Cellular and Developmental Biology
Editor
Michael Fitzsousa
Director of Communications
Managing Editor
John Curtis
Contributing Editors
Janet Emanuel, ph.d.
Peter Farley
Jennifer Kaylin
Karen Peart
Cathy Shufro
Jacqueline Weaver
Marc Wortman, ph.d.
Contributors
Terry Dagradi
John Dillon
Ariane Kirtley, m.p.h. ’04
Jill Max
Pat McCaffrey, ph.d.
Pem McNerney
Carol Milano
Kara A. Nyberg, ph.d.
Richard Rapport, m.d.
Colleen Shaddox
Copy Editors
Rebecca Frey, ph.d.
Michelle Komie
Anne Sommer
Mailing List Inquiries
Claire M. Bessinger
Communications Coordinator
Cheryl R. Violante
Website Coordinator
Design
www.daphnegeismar.com
Printing
The Lane Press
Yale Medicine is distributed to alumni,
faculty, students and friends of the
School of Medicine, as well as leaders
in Yale University alumni activities.
Abbreviations commonly used in Yale
Medicine include hs to denote the final
year of residency for house staff, fw for
the final year of a fellowship, eph for the
Department of Epidemiology and Public
Health and School of Public Health
and ynhh for Yale-New Haven Hospital.
Postal permit held by Yale University,
155 Whitney Ave., New Haven, CT 06520
Copyright © 2007 Yale School of Medicine
All rights reserved.
address correspondence to
Editor, Yale Medicine
300 George Street, Suite 773
New Haven, CT 06511
Telephone: 203-785-5824
Facsimile: 203-785-4327
Electronic mail: ymm@yale.edu
Website: http://yalemedicine.yale.edu
starting point
3
Water, a jumping gene and Paul Beeson
This past spring we heard from Ariane Kirtley, m.p.h. ’04, who
grew up in Africa and returned there after her graduation.
Our cover story—her account in words and photographs—
describes the life of the Tuareg and Woodabe inhabitants of
the Azawak, the remote and drought-stricken plains in Niger
where life is a constant search for water. But Kirtley is not
content with simply documenting living conditions there—
she has also formed a foundation to help build wells in the
region and save not only lives but a pastoral way of life as well.
Closer to home, Tian Xu, ph.d., professor and vice
chair of genetics, has found a faster and cheaper way of
making knockout mice. It involves a transposon, a “jumping gene” from a moth that can be inserted into the mouse
genome, and a complex process that allows the laws of
genetics to run their course with a little tweaking from
human hands. This first transposon to be effectively used
in mammals allows scientists to knock out known genes
and discover others previously unknown. Freelance writer
Pat McCaffrey spent some time with Xu to learn how
S E CO N D O P I N I O N B Y S I D N EY H A R R I S
he hopes to use his technology to help scientists find the
causes of disease on a grand scale.
Last August we learned of the passing of Paul B.
Beeson, m.d., who served as chair of internal medicine
from 1952 to 1965. During his tenure he hired new faculty,
inspired his staff and residents and built the department
into one of the best in the country. Renowned internationally
as both a scientist and clinician, Beeson made fundamental
contributions to the understanding of fevers and infectious
diseases. Richard Rapport, m.d., author of Physician: The Life
of Paul Beeson, has graciously allowed us to excerpt sections
of his biography that deal with Beeson’s time at Yale.
John Curtis
Managing Editor
john.curtis@yale.edu
4
chronicle news from cedar street
New funding paradigms
reshape research
lasse skarbövik
Despite a tougher climate for NIH
dollars, school gets its largest grant
ever as part of Roadmap initiative.
Flat funding and a new research paradigm have turned federal funding of
medical research on its head. After
the recent doubling of the budget of
the National Institutes of Health (nih),
funding has leveled off, resulting in a
net decrease thanks to inflation. And
the nih is shifting the remaining dollars away from lone investigators to
multidisciplinary teams of scientists.
Both trends are being felt at the
School of Medicine. In October the
school received its largest nih research
grant ever, a $57.3-million Clinical and
Translational Science Award (ctsa),
a new grant designed to encourage
interdisciplinary research and the rapid
movement of laboratory findings
into human studies.
The award, one of 12 made around
the country, will “transform how
clinical and translational research is
conducted,” said nih Director Elias
A. Zerhouni, m.d.
The ctsa fits in with the nih Roadmap for Medical Research, which
calls for reshaping clinical research to
accelerate medical discovery. It also
fits in with the medical school’s own
planning, said Dean Robert J. Alpern,
m.d., Ensign Professor of Medicine.
“A strategic planning initiative we
launched in 2004 identified clinical
research as a top priority and established the Yale Center for Clinical
Investigation (ycci), a focal point for
translational research,” Alpern said.
“The ycci’s structure, which builds on
Yale’s strengths in education, basic
science and community-based research,
is virtually identical to the vision put
forth by the nih in this new program.”
“With the ctsa grant we will be able
to train many more clinical investigators, known as ycci Scholars, who
will be well-equipped to assemble the
expert interdisciplinary teams they
need to do top-quality translational
research,” said Robert S. Sherwin,
m.d., ycci director and principal investigator on the ctsa grant.
Meanwhile, scientists at Yale and
other universities are finding grants
harder to acquire. Over the last two
years, said Carolyn W. Slayman, ph.d.,
deputy dean for academic and scientific affairs, Yale’s success rate has
fallen, in line with national trends, but
it is still above the national average.
“Some labs might have to cut back
on the number of people in the lab,
making it more difficult to complete
projects,” said Lynn Cooley, ph.d.,
professor of genetics and cell biology
and director of the Combined Program
in the Biological and Biomedical
Sciences. “Students and postdocs in
training contribute enormously to
research excellence in their labs. Both
valuable research and the pipeline
of new research talent are threatened
by these budget cuts.”
Slayman said the medical school’s
Grants and Contracts Office, working
with the development staff and with
the Office of Cooperative Research, is
providing information on alternative
funding, including nonfederal granting
agencies, foundations and corporations.
She said these efforts have met with
some success—direct grant dollars to
Yale researchers increased by 5.9 percent last year.
“We are working closely with department chairs and program directors
to provide as much help as possible to
faculty members who run into difficulty
with grant support,” Slayman said.
—Pem McNerney and John Curtis
5
University hopes to build
on success in campaign for
“Yale Tomorrow”
Nearly a decade after the close of its last
major fund-raising campaign, Yale has
begun a five-year drive to raise $3 billion, a major portion of which will be
directed toward science and medicine.
At the public launch of the “Yale
Tomorrow” campaign on September 30,
President Richard C. Levin announced
that donors have already committed
$1.3 billion in gifts and pledges during its quiet phase, which began in
mid-2004.
The public campaign kicked off with
a day of presentations by noted faculty
and alumni—including medical school
professors Irwin M. Braverman, m.d. ’55;
hs ’59, fw ’62; Christopher K. Breuer,
m.d.; Carolyn M. Mazure, ph.d.; Milissa
A. McKee, m.d.; R. Lawrence Moss,
m.d.; W. Mark Saltzman, ph.d.; Bennett
A. Shaywitz, m.d.; Sally E. Shaywitz,
m.d.; and Tian Xu, ph.d.—followed by
a multimedia program narrated by actor
Sam Waterston, a 1962 Yale College
alumnus, and a gala dinner in University Commons.
The campaign is organized around
four major priority areas: “Yale College,”
“The Arts,” “The Sciences” and “The
World.” In the sciences Yale will seek
support for programs focused on
translating basic science insights into
clinically relevant work. Among the
priorities are programs in neural degeneration and repair, stem cell biology,
translational immunology, functional
genomics and clinical investigation.
The ultimate goal is to find new and
better methods of diagnosing and
treating illness, said medical school
Dean Robert J. Alpern, m.d., Ensign
Professor of Medicine.
According to Inge Reichenbach,
Yale’s vice president for development,
the campaign has set specific goals for
the medical school, including the establishment of new endowed professorships, financial aid for students, new
buildings for research and clinical care,
technology resources, educational innovation and support for the cancer hospital addition to Yale-New Haven Hospital.
The drive comes at a time when the
university is enjoying record growth
in its endowment, which grew from
$5.8 billion in 1997, at the conclusion
of the university’s “… and for Yale”
campaign, to $18 billion for the fiscal
year ending June 30. During that
same nine-year period, the medical
school’s endowment has risen from
$446.6 million to $1.5 billion. The
university has an operating budget of
$1.67 billion for 2006-2007, of which
$676 million is expected to come from
the endowment.
But the size of the endowment, second only to Harvard’s $29 billion nest
egg, does not mean the university has
all the resources it needs to grow in
new directions, according to campaign
leaders. “To expand Yale beyond its
current scale and scope, to build the
Yale of tomorrow, we will need new
financial resources,” said President
Levin. “Above all, we need to complete
the transformation of Yale from a local
to a regional to a national to an international university.”
Yale’s wealth is an issue that fundraising staff must address directly with
potential donors, said Jancy Houck,
m.a., who became the university’s associate vice president for development
and director of medical development
and alumni affairs on September 18.
Income from the current endowment
was committed to specific items at the
time of the original gift decades or more
ago, she said. “It takes new resources
to do new things,” said Houck.
The same is true with grant dollars
that come from the federal govern-
ment, foundations and corporations,
she added. For example, the $57.3million Clinical and Translational
Science Award (ctsa) that the medical
school received in October (see related
story), the largest grant ever received
by the school, also presents an opportunity to engage donors in conversations about the medical school’s future.
“This support from the National
Institutes of Health doesn’t take
away from our need for philanthropy,
because grants are very, very specific.
You have to use the funding in the
exact manner outlined in the proposal,” said Houck. “The philanthropy
that we would be looking for would
be for items that are not included in a
big grant, where people could really
leverage their gift, knowing that there
is a certain amount of activity that is
going to take place already.”
—Michael Fitzsousa
6
chronicle
Years after gas attack, the
horror lingers in an Iranian
town, eph alumna finds
fa r a h n a z fa l a h at i
After every bombing, people in Sardasht,
a small town at the foot of Iran’s
Zagros Mountains, ran outside to help
the injured. On June 28, 1987, they
rushed into a world that smelled of
garlic. The air burned like acid. Bodies
were covered with blisters. Children
were crying, beyond comfort. When
After an interview in Rabat, a Kurdish town in
Iran that endured high-intensity warfare
during the Iran-Iraq war, Farnoosh Hashemian,
right, posed with some of the women she
interviewed.
the blindness came, the villagers had
no reason to expect that it would be
temporary. For many, it was not.
The physical effects of chemical
weapons like the mustard gas that fell
on this Iranian town during the 19801988 war between Iran and Iraq are
well-documented: burns, respiratory
problems and temporary or permanent
blindness. A new Yale study now
sheds light on the psychiatric effects.
Farnoosh Hashemian, m.p.h. ’05, a
research associate in the Department
of Epidemiology and Public Health
(eph), has documented severe and
long-term mental health problems in
Sardasht residents who survived a
chemical attack. Her data were so compelling that the Iranian government
made a psychologist, a scarce resource
in the country, available to the 4,000
chemical-attack survivors in Sardasht.
Hashemian’s team published
their findings in the August 2 issue of
JAMA: The Journal of the American
Medical Association. They collected data
in three Kurdish towns in rural Iran:
one was bombed 10 times; another
was bombed 75 times; and a third,
Sardasht, was bombed 60 times and
also was attacked with chemical
weapons. Hashemian did not anticipate the magnitude of distress she
found in Sardasht— 59 percent of
those exposed to chemical weapons
had experienced post-traumatic stress
disorder, and 33 percent were still
suffering from the disorder. She found
that 65 percent had major anxiety
symptoms and 41 percent had severe
depressive symptoms.
Growing up in Tehran during the
war, Hashemian knew that Saddam
Hussein had gassed civilians and
Iranian troops. “Will he gas Tehran?”
the adults whispered. Believing a
chemical attack on the Iranian capital
was imminent, her family fled the
city, eventually settling in Canada.
Three years ago Hashemian returned
to Iran as an eph student on a Downs
International Health Student Travel
Fellowship. Although the program usu-
ally sends students to countries unfamiliar to them, Hashemian convinced
the review committee that rural Kurdish
areas would constitute a new culture
for a woman raised in fast-paced
Tehran. Her parents in Canada were a
harder sell. The border region in
northern Iran is known for smugglers
and land mines. “They were very
worried, but now they are proud of
me,” she said.
Hashemian collected data along
with Farahnaz Falahati, m.d., a
physician with the Janbazan Medical
and Engineering Research Center,
the Iranian equivalent of the Veterans
Administration. The women stayed
in spartan quarters with no showers or
kitchen. But Hashemian said their
main challenge was hearing the dreadful and grim stories.
Survivors reported nightmares,
inability to work and relationships broken under the weight of stress. They
believed another attack would come at
any moment. Their fear was heightened during Hashemian’s visit because
the United States had just invaded Iraq.
Many villagers expected that Saddam
would gas them again in retaliation for
the U.S. attack. Despite their fearfulness, they invited the researchers into
their small houses, offered them special
meals and willingly told their stories.
“They felt that they had been forgotten,” Hashemian explained, and she
agrees. The international community
was silent during and after the attacks,
she said.
Hashemian would like to see her
work used by international organizations seeking to eradicate chemical
weapons. By documenting the suffering of civilians—who account for most
war casualties—Hashemian said,
public health professionals can raise
discussions of war and peace above
the realm of politics. “War is a serious
public health issue.”
—Colleen Shaddox
7
Stem cell program gets
under way at Yale with
arrival of cell biologist
terry dagradi
One of the nation’s leading stem cell
biologists arrived at Yale last summer
to lead a new program that will explore
the unique properties and therapeutic
potential of these cells. Haifan Lin,
ph.d., and Associate Director Diane
S. Krause, m.d., ph.d., an associate
professor of laboratory medicine and
pathology and an expert on bone marrow stem cells, will lead the new Yale
Stem Cell Program (yscp). They will
oversee a group of a half-dozen scientists and an administrative and technical staff devoted to research on human
embryonic and adult stem cells, as
well as stem cells in the mouse, fruit
fly and roundworm.
The new center comes as the State
of Connecticut has allocated $20 million for the Connecticut Stem Cell
Research Grants Program, making it
one of three states to fund this research.
The yscp has applied for funding from
the state program and its applications
were still under review this fall.
Stem cells, which can differentiate
into many of the myriad cell types that
form the body’s tissues and organs,
have been much in the news as a
potentially powerful treatment for diabetes, Parkinson’s disease, heart disease, spinal cord injury and other
serious illnesses. The program will
provide a scientific hub for more than
Haifan Lin is leading a new scientific center for
faculty working on stem cell-related projects.
30 faculty members across the medical
school and university who work on
stem cell-related topics. Over the next
few years, the yscp will recruit four
additional faculty members.
Three core research facilities are
now being put in place: a human
embryonic stem cell culture laboratory
directed by Lin and Krause; a cell
sorting center directed by Mark J.
Shlomchik, m.d., ph.d., professor of
laboratory medicine and immunobiology; and a confocal microscopy
laboratory directed by Michael H.
Nathanson, m.d., ph.d., professor of
medicine and cell biology. The yscp
will eventually occupy one floor of the
Amistad Building on the southern
edge of the medical school campus,
which is now under construction and
slated for occupancy next year.
Lin comes to Yale from Duke University, where he was co-founder and
co-director of the Stem Cell Research
Program. He received his undergraduate degree from Fudan University in
Shanghai, China, and his ph.d. from
Cornell University in 1990. He completed his postdoctoral training at the
Carnegie Institution of Washington
before joining the Department of Cell
Biology at Duke University Medical
Center in 1994.
Through his discovery of stem
cells in the ovary of the fruit fly and his
establishment of these cells as a research
tool, Lin obtained direct evidence for the
century-old hypothesis of asymmetric
division as the means by which stem
cells can both self-renew and produce
daughter cells with the ability to differentiate into many distinct cell types.
Lin has also discovered key genes that
regulate stem cell division.
“Haifan Lin is a pre-eminent scientist whose research on the most basic
mechanisms of stem cell biology has
had a tremendous impact on the field,”
said Dean Robert J. Alpern, m.d.,
Ensign Professor of Medicine. “He has
the broad perspective needed to lead
this exciting new effort at Yale.”
—Peter Farley
et cetera • • •
YA L E L I C E N S E S A I D S D R U G
Yale University concluded in June a license
agreement granting Oncolys BioPharma of
Tokyo exclusive rights to develop a new compound to treat hiv. Yale has also applied for
a patent for the compound, Ed4T. Preclinical
studies have already begun, and Oncolys
BioPharma hopes to begin Phase I/II clinical
trials in 2008.
Ed4T is a thymidine analogue that blocks
reverse transcriptase, an essential enzyme
for viral replication. The compound was discovered and developed jointly by researchers
in Japan and Yung-Chi Cheng, ph.d., the
Henry Bronson Professor of Pharmacology
at Yale.
Pharmacological studies have shown that
Ed4T has more potent anti-hiv activity than
existing nucleoside-analogue reverse transcriptase inhibitors (nrtis) and is active
against viruses that are resistant to the existing nrti and non-nrti drugs. Further, Ed4T
does not affect dna synthesis in mitochondria, a toxic side effect of some nucleotide
analogues. These findings suggested that
Ed4T might offer unique therapeutic advantages over existing anti-hiv drugs.
—John Curtis
N E W M R SY ST E M AT YA L E
Yale will receive a $2 million High-End Instrumentation (hei) grant from the National
Center for Research Resources (ncrr) to buy
a 7-Tesla human magnetic resonance (MR)
system that will facilitate ultra-high resolution studies of diabetes, epilepsy, psychiatric
disease and learning disorders. The ncrr
makes one-time awards to support the purchase of sophisticated instruments costing
more than $750,000 to advance biomedical
research and increase knowledge of the
underlying causes of human disease. Douglas
L. Rothman, ph.d., professor of diagnostic
radiology and biomedical engineering, will
oversee the MR system, a shared resource for
several investigators funded by the National
Institutes of Health. Yale has recruited two
new faculty members to develop new methods of biochemical image-guided neurosurgery using the system.
—J.C.
8
rounds medicine and health at yale
Consistency lacking in
transfer of patient data
Many hospitals don’t have protocols
for passing patient information among
doctors, Yale study finds.
No matter how swift the runners, a
relay race is lost if they don’t pass
the baton properly. A new Yale study
finds that patient care is a baton at
increasing risk of being dropped
because too many internal medicine
residency programs lack systems
for transmitting patient information
from shift to shift.
Communication failure is one of
the chief causes of medical errors, studies have found, and the transfer of
care is a weak link in the chain. But the
Yale study, published in the Archives
of Internal Medicine in June, finds that
many hospitals lack an established protocol for passing on patient informa-
tion, even though transfers, also known
as sign-outs, are becoming more common as residents work fewer hours.
“Communication is not something
that the layman thinks is a problem,”
said Leora I. Horwitz, m.d., a postdoctoral fellow in internal medicine
and the study’s lead author. However,
patients are now under the care of
more doctors, due to limits on residents’
workweeks. Transfers “happen routinely
and have the potential for catastrophe,”
she said.
Hospitals should have a standardized system each time a doctor
hands off a patient to another doctor,
Horwitz said.
Horwitz’s team investigated the signout practices at 202 internal medicine
residency programs in the United
States and the impact of the reduced
workweek on patient transfer protocols. Patient transfers, they found, rose
11 percent—to an average of twice
daily in a four-day hospital stay—since
the regulations took effect in 2003.
The procedures for those handoffs
varied widely, though. Fifty-five percent
of the programs didn’t require doctors
to pass on key patient information in
both oral and written form, which
Horwitz said would curtail the risk for
errors. In six of 10 programs, nurses
were not informed that a transfer had
occurred, and in many programs no
workshops or lectures on sign-out
skills were offered. In 34 percent of the
cases, the handoff was left to interns
alone. And fewer than a fifth of the
programs used a Web-based program,
or forwarded pager messages in the
transfer process.
“If you’re the primary doctor, you’re
much less likely to make a preventable
error than if you’re covering that person just for a day and you don’t know
that [patient] well,” Horwitz said. An
oral transfer allows the new doctor to
ask questions or give “readback”—
like a pilot would give to an air traffic
controller. Written information can
be referred to later if needed.
The sign-out can differ from hospital to hospital, but it needs to be consistent within the health care organization, said Paul M. Schyve, m.d., senior
vice president of the Joint Commission
on Accreditation of Healthcare Organizations, which made sign-outs one of
its chief patient safety goals for 2006.
“A standardized approach makes it
easy for people to ask and respond to
questions,” he said.
The survey didn’t examine whether
the various approaches to sign-outs
actually prevent medical errors, especially in light of the shorter workweek.
“There’s a lot of anxiety around workhour limitations in terms of whether
they increase discontinuity enough
that it overwhelms the benefits of
physicians being rested,” Horwitz said.
Future studies will decide “whether
that’s clinically significant or not.”
—John Dillon
9
New forum offers a place for
doctors and nurses to discuss
issues of patient care
terry dagradi
On a Thursday afternoon last fall, 23
physicians, nurses and social workers
at Yale-New Haven Hospital (ynhh)
met to discuss a case that made
everyone uncomfortable: a patient
with colon cancer suffered serious and
eventually fatal complications following surgery, and the patient’s daughter
refused to leave her side or her room
during the two-month hospital stay.
The daughter would not allow staff to
communicate directly with her mother
and slept much of the day in the hospital room, denying access to nurses
even when they attempted to administer medications or other care.
The discussion was part of the
Schwartz Center Rounds, a program
that creates a forum for caregivers to
discuss complex emotional and social
issues involved in caring for patients.
In 1995, Kenneth B. Schwartz, a health
care attorney in Boston, was dying
of lung cancer. He was fortunate to
receive not just top-notch medical care,
but also an attention to his comfort
and quality of life that made his illness
easier to cope with for himself and his
Health care professionals at ynhh can discuss
complex issues of patient care during Schwartz
Center Rounds, a national program.
family. Shortly before his death, he
established the Kenneth B. Schwartz
Center, a nonprofit organization that
has been helping caregivers provide
compassionate care to their patients
since 1997. The Schwartz Center
Rounds now operate in approximately
100 hospitals in 25 states; the program
was brought to the Yale Cancer Center
last February as part of a larger effort
to increase the focus on supportive
care for patients with severe illness.
“It’s a unique forum for talking
about difficult and challenging situations in a nonmedical fashion,” said
Kenneth D. Miller, m.d., assistant professor of medicine (medical oncology),
director of supportive care programs
at the Center and the rounds leader for
the program. Open to all ynhh staff,
the rounds take place once a month
and feature a presentation by a medical
team followed by a group discussion.
Past topics of the Schwartz Center
Rounds have included obtaining
informed consent from mentally ill
patients; keeping hope alive; and
what to do when the patient, doctor
and family are not on the same page.
“We’re trying to develop a broader
view on how different patients, and
different families cope with really difficult situations that may be different
than what we might have chosen for
ourselves or what we think we’d
choose,” Miller said.
According to Marjorie Stanzler,
director of programs for the Schwartz
Center, the ability of caregivers to
voice their concerns in a safe environment translates into new insights into
caring for patients, an appreciation
of the problems faced by colleagues in
other disciplines and the realization
that they are not alone in dealing with
troublesome circumstances.
—Jill Max
ST R O K E , H E A RT AT TA C K A N D F I R I N G
Losing a job just as retirement approaches
more than doubles the chances of a heart
attack or stroke, according to a Yale study
published in Occupational and Environmental
Medicine in June.
For over 10 years researchers observed
more than 4,000 people who were between
the ages of 51 and 61 when the study began
in 1992. During that period 582 lost their
jobs. An earlier six-year study of the same
people had suggested a higher risk of stroke,
but didn’t make a definitive link between
job loss and heart attacks. “With longer
follow-up ... on heart attack and stroke events
we were able to better assess the association between employment separation and
the medical outcomes,” said William T.
Gallo, ph.d., the lead author and an associate research scientist in the Department
of Epidemiology and Public Health.
“We do a lot of downsizing in our country and older individuals are often affected,”
said co-author Elizabeth H. Bradley, m.b.a.,
ph.d., professor of public health. “We need
to recognize not only the economic consequences, but also the health consequences.”
—John Curtis
K I D N E Y PAT I E N T S L E F T O U T O F T R I A L S
Although at high risk for cardiovascular
death, patients with chronic kidney disease
(ckd) are frequently left out of cardiovascular trials, School of Medicine researchers
reported in the September 20 issue of
jama: The Journal of the American Medical
Association.
The researchers’ review of 153 clinical
trials published between 1985 and 2005
found that patients with kidney disease
were excluded from 56 percent of the trials
and were more likely to be excluded from
multicenter trials. Cardiovascular death
is the leading cause of death in patients
with ckd.
“Inclusion and reporting of kidney disease patients in cardiovascular trials must
improve,” said senior investigator Chirag
Parikh, m.d., assistant professor in the Section
of Nephrology. “Alternatively, we need
to design separate trials for cardiovascular
treatment exclusively in ckd patients.”
—J.C.
findings from the bench
An early start for the
thinking brain
Yale scientists discover predecessor
cells that pave the way for the
cerebral cortex.
The cerebral cortex, a layer of cells just
a few millimeters thick on the outermost surface of the brain, is largely
what makes humans noble in reason
and infinite in faculties. New research
from the School of Medicine shows
that developing embryos, in their haste
to become quintessentially human,
generate the first neurons of the cortex
only 31 days after fertilization—much
earlier than previously thought.
The cerebral cortex is an evolutionary marvel. Its distinctive convoluted
shape arose because the size of the cortex expanded disproportionately in
relation to the rest of the brain during
evolution. The 20 billion neurons
packed within the cortex’s smooth gray
folds account for about 40 percent of
the brain’s weight, and the connections
among them are largely responsible
for the functions considered unique to
humans, such as memory, thought,
perceptual awareness, language, intellect and consciousness.
Using precise cellular markers,
Pasko Rakic, m.d., ph.d., the Dorys
McConnell Duberg Professor of
Neurobiology and professor of neurology, and chair of neurobiology and
colleagues have discovered “predecessor” neurons that first appear in
human embryos before the neural
tube, the precursor of the central
nervous system, has completely
closed and before eyes, arms and legs
begin to bud. According to Rakic,
these predecessors could well be one
type of neural stem cell of the “thinking brain.”
Until recently, researchers thought
that all cortical neurons arose within
a rudimentary cortical nexus and then
migrated radially, like spokes jutting
out from an axle, into place. However,
Rakic’s findings show that the predecessor neurons arise from basal layers
within the developing brain and then
travel through inner cell layers to reach
the cortex. The precocious cells generate long extensions that pull them
to different locations as the brain develops. These extensions may also act
as scaffolds to guide late-blooming cortical neurons to their proper locations.
In the July issue of Nature Neuroscience, the researchers wrote that
studying how predecessor cells help
to wire the billions of neurons of the
adult human cortex may provide new
insights into how humans differ from
more primitive species and may shed
light on the causes of mental illness.
“Unraveling the early development
of this complex structure,” the team
wrote, “might provide the key to
understanding both the mechanisms
underlying its expansion during evolution and the pathogenesis of many
cognitive disorders.” Rakic added, “If
we want to repair the human brain,
we have to know how the human cortex develops; we have to know the
timing, the sequence and the type of
cells involved.”
Rakic said that the next goal is to
determine which genes are switched
on in predecessor cells to control early
cortex development. If the predecessors are indeed neural stem cells, identifying the genes responsible for early
b y st r o n , r a k i c , m o l n a r a n d b l a k e m o r e
10
Yale scientists have identified the first neurons
(the golden area in the image) in the embryonic
human cerebral cortex, which appear only 31
days after fertilization. This is much earlier than
previously thought, and the discovery of these
predecessor cells in the part of the brain responsible for such human attributes as memory, language and intellect may provide insights into
mental illness.
cortex formation could provide insight
into ways to generate new cortical neurons to repair brain injury. The team
also plans to identify the source of
predecessor cells by performing experiments in nonhuman primates that
will enable them to visualize neuron
migration using modern microscopy
techniques.
These findings will bring researchers
one step closer to understanding the
developmental mechanisms responsible
for creating the thinking brain. “I am
fascinated with the idea that I use my
cortex to look at the cortex itself to determine what makes it possible for me to
think,” said Rakic.
The project, supported by the Kavli
Institute for Neuroscience at Yale,
involves collaborations with societies in
England and Russia.
—Kara A. Nyberg
11
Lacking an enzyme linked to
diabetes and obesity, mice stay
slim on a high-carb diet
e i n at p e l e d
Even on a “supersize” diet, mice bred
to lack a certain enzyme remained
more svelte than mice with the enzyme,
according to a study by Yale scientists
in the July 2006 issue of the journal
Cell Metabolism. Moreover, in a finding
that surprised the research team, the
mice’s blood sugar levels remained
under control.
The study’s senior author cautioned
against premature talk of an elixir that
prevents diabetes or does away with the
need for exercise. “The long-term goal,
I think, would be to figure out how this
enzyme is working under normal circumstances,” said Anton M. Bennett,
ph.d., associate professor of pharmacology. “But I think we’re a long ways
away from this as an obesity target.”
Bennett’s laboratory studies mitogenactivated protein kinase phosphatases
(mkps), important players that have
been implicated in numerous cellular
functions such as cell growth and cell
survival. For a better understanding of
these enzymes, mice were bred to lack
one of them, mkp-1. “There was no
preconceived hypothesis that it would
necessarily be involved in regulating
body mass,” Bennett explained.
At first there appeared to be no obvious differences between the mice lacking mkp-1 and the control mice. “If you
looked in the cage and had the mice
side by side, they would be indistinguishable,” Bennett said. Both groups
ate a typical chow diet—“the equivalent
of three squares a day.” Soon, the
knockout mice showed that they were
less likely to put on the ounces.
“Then we put them on a McDonald’s
‘supersize’ equivalent, where 55 percent of the calories was from carbohydrates,” he continued. “The differences
in weight were extremely pronounced.”
The mice without the enzyme were,
on average, 15 to 20 percent leaner
than the control group. “The enzyme
seems to act as a brake on how fast you
burn energy. When you remove that
enzyme, energy expenditure seems to
go up dramatically.”
The mice without the enzyme were
also better able to control their glucose
levels. Because they were leaner, they
also should have exhibited signs of
increased insulin sensitivity. “But it
was normal,” Bennett said. “That was
somewhat of an unexpected result.”
The knockout mice also were less likely
to show signs of metabolic syndrome,
a constellation of risk factors for heart
disease and diabetes. One of the hallmarks of metabolic syndrome is a fatty
liver, and the mice without the enzyme
were resistant to that symptom.
While the study shows that mkp-1
“may contribute to obesity and diabetes,” it is far from certain whether
turning it off will prevent or ameliorate
those conditions. There is also concern
about the overall effect of turning off
the enzyme in the body. Bennett said
studies have found knockout mice to
be more susceptible to infection.
“That’s not a good thing,” he said.
“Everything is connected.”
—John Dillon
S M O K I N G A N D N I COT I N E R E C E P TO R S
Smokers may have a hard time quitting
because their brains have significantly more
nicotine receptors than those of nonsmokers,
according to a study by Yale researchers
published in August in the Journal of Neuroscience. The study, funded by the National
Institute of Drug Abuse, is believed to be the
first to offer direct evidence in living smokers
that the numbers of the most common
nicotine brain receptors are higher during
early abstinence from smoking.
“Nicotine craving is an important factor
associated with relapse,” said Julie K. Staley,
ph.d., associate professor of psychiatry
and diagnostic radiology and lead author of
the study. “This study paves the way for
determining whether medications normalize
the number of receptors and why some
smokers, such as women and those with
neuropsychiatric disorders, have more difficulty quitting smoking.”
Staley said the team used spect imaging
to see how the nicotine receptors adapt
in response to the repeated stimulation of
smoking a cigarette.
—John Curtis
T E STO ST E R O N E V S . N E R V E C E L L S
A study by Yale scientists has shown that
a high level of testosterone—such as that
caused by the use of steroids—can lead to
the death of brain cells. “Next time a musclebound guy in a sports car cuts you off on
the highway,” said senior author Barbara E.
Ehrlich, ph.d., professor of pharmacology
and cellular and molecular physiology, “don’t
get mad, just take a deep breath and realize
that it might not be his fault.”
Previous studies have shown that large
doses of steroids can cause hyperexcitability,
an aggressive nature and suicidal tendencies, which could mean alterations in neuronal function caused by the steroids. “In the
present study we have demonstrated for the
first time that the treatment of neuroblastoma cells with elevated concentrations of
testosterone for relatively short periods, six
to 12 hours, induces a decrease in cell viability by activation of a cell death program,”
said Ehrlich, whose study appeared in the
Journal of Biological Chemistry in September.
—J.C.
12
books & ideas bookshelf
Bruce Wexler’s new book explores
neural processes and how they
influence psychological and social
processes.
Culture and the brain
Bruce E. Wexler, m.d., professor of psychiatry, believes that
understanding how our brains work can illuminate human
experiences small and large—from why our favorite letters
in the alphabet are those in our own names to why we must
struggle to adjust when a loved one dies. In his new book,
Brain and Culture: Neurobiology, Ideology, and Social Change,
he summarizes contemporary research into the brain and
how it explains why we resist the unfamiliar and the alien—
whether it’s a colorful tattoo on our teenager’s biceps or the
rhetoric of those who insist theirs is the only true religion.
“The aim of this book is to look at what we know about
neural processes to see if that can increase our understanding of the psychological and social processes that rest
upon this neurobiological platform,” said Wexler, a clinician
and researcher at the Connecticut Mental Health Center.
“Our appreciation of the neurobiology can help us to understand—and eventually deal with—both psychological and
social issues.”
The connections between neurons that create networks
derive not only from our genes but also from sensory input
when we’re young. And human neural networks remain
plastic into the third decade of life, much longer than those
of any other animal.
The less flexible adult human brain strives to see the
world in a way that “agrees with internal structures.” That’s
why physicians evaluating a sick patient may choose a common diagnosis even when the patient’s problems don’t quite
fit. “We complete perceptions in keeping with our expectations, and those expectations are based on past experience,
but not necessarily on the facts at hand,” Wexler observed.
It is the comfort of the familiar that motivates some immigrants to settle in ethnic enclaves, Chinatowns and Little
Pakistans that recreate their former homes. The generation
gap is especially poignant for immigrants, whose children
are shaped by a very different world from the one in which
they grew up. And for all parents, the world changes from
generation to generation. “Most children in the world today
are raised almost entirely in human-made environments,”
Wexler said. Because each new generation has different
j o h n c u rt i s
A new book explores the links between neural networks,
feelings and culture.
brains from those of their parents, they in turn raise their
children differently—leading to what Wexler calls “transgenerational shaping of brain function.” But the generation
gap discomfits all parents, because children loom large in
parental neural networks.
“We don’t like our children to turn into foreigners, because
our children are so richly represented within us,” said
Wexler. Similarly, we have trouble adapting when a loved one
dies, because that person occupied a central place in our
neural networks. “It’s a very arduous task to restructure, and
it takes adults about a year.”
What he calls “the neurobiological antagonism to difference” can help explain violent cultural clashes: genocide
in Armenia, Germany and Bosnia; massacre in Rwanda;
Christians warring against Muslim “infidels;” and Muslims
attacking Western “infidels.”
Understanding our resistance to differences can point
the way to reconciliation. Wexler now spends most of his
spare time working for a nonprofit group he started called
A Different Future. Its aim is to “amplify the voices” of
Arabs and Israelis advocating peace—delivering a message
of mutual respect that will embed itself into the neural
networks of young Israelis and Palestinians.
Wexler admits that even his own neural networks may
balk at the unfamiliar. On a trip though Ohio he saw a
building that looked out of place. He remembers thinking,
“What is a mosque doing here?”
—Cathy Shufro
Bookshelf focuses on books and authors at the School of Medicine.
Send suggestions to Cathy Shufro at cathy.shufro@yale.edu.
13
book notes
Play Ball with Me!
by Lynn Reiser, m.d. ’70, clinical
professor of psychiatry (Alfred
A. Knopf) This interactive picture
book of guessing games introduces young readers to various
ballgames through the recognition of simple objects.
Social Structures, Aging, and
Self-Regulation in the Elderly
with contributions by Becca R.
Levy, ph.d., associate professor
of epidemiology and psychology; edited by K. Warner Schaie,
ph.d., and Laura L. Carstensen
(Springer Publishing Company)
Contributors to this book explore
how societal contexts influence
aging and how self-regulation
at the most basic levels of functioning influences the physical
health and economic circumstances of people as they age.
Principles of Molecular
Medicine, 2nd ed.
with contributions by Jean
Bolognia, m.d. ’66, professor
and vice chair of clinical affairs
(dermatology), Daniel Goldstein, ph.d., assistant professor
of medicine (cardiology), and
Stephen M. Strittmatter, m.d.,
the Vincent Coates Professor
of Neurology and professor of
neurobiology (Humana Press)
This volume contains new sections on genetics, oncology
and metabolic and infectious
diseases. The authors discuss
the latest findings about links
between genetic mutations and
diseases; genomic approaches
to a variety of diseases; the
potential of stem cells to regenerate muscle, heart and neural
cell populations; and advances
in the understanding of the
biology of such previously untreatable neurodegenerative
diseases as Huntington’s.
Aglow in the Dark:
The Revolutionary Science
of Biofluorescence
by Vincent A. Pieribone, ph.d.,
associate professor of cellular
and molecular physiology and
neurobiology, and David F.
Gruber (Belknap Press) This
book describes the human fascination with bioluminescence, or
“living light.” It follows the path
to one of the groundbreaking
discoveries of the 20th century—
green fluorescent protein, the
glowing compound that has revolutionized molecular biology.
dna Vaccines: Methods and
Protocols, 2nd ed.
by W. Mark Saltzman, ph.d., the
Goizueta Foundation Professor
of Chemical and Biomedical
Engineering and professor of
cellular and molecular physiology, Janet L. Brandsma, ph.d.,
associate professor of comparative medicine and pathology,
and Hong Shen, ph.d. (Humana
Press) This five-part volume
contains state-of-the-art information about dna vaccine
technology. Part I contains dna
vaccine design protocols, focusing on methods that achieve
optimal expression in host cells.
Part II presents methods for
dna delivery. Part III discusses
methods for enhancing the
potency of dna vaccines. Part IV
describes several key areas of
application in the field, including allergy, avoidance of autoimmunity, and neonate and infant
vaccine response. The book concludes with a review of protocols for vaccine production and
purification, and quality control
methods.
College Life 102: The No-Bull
Guide to a Great Freshman Year
by Andrew G. Kadar, m.d. ’73
(iUniverse) The author offers
advice to newly arrived college
students on how to succeed
both inside and outside the
classroom. Tips include how to
dodge the stress of deadlines,
enroll in classes after they’re
officially filled, avoid the “freshman 15” and get better grades
by studying smarter rather than
harder. The book also provides
information about nutrition, illegal drugs, contraception and tattoos and piercings.
Hematology: Basic Principles
and Practice, 4th ed.
by Edward J. Benz Jr., m.d., fw
’79, Ronald Hoffman, m.d.,
Sanford J. Shattil, m.d., Bruce
Furie, m.d., Harvey J. Cohen,
m.d., ph.d., Leslie E. Silberstein,
m.d., and Philip McGlave, m.d.
(Churchill Livingstone) This book
covers the basic scientific foundations and clinical aspects of
hematology. It provides practitioners with comprehensive and
up-to-date information on hematology that reflects the rapid
change in the molecular and cellular areas of the specialty.
Immunology of Pregnancy
by Gil Mor, m.d., associate professor of obstetrics, gynecology
and reproductive sciences
(Springer) This text reviews current knowledge about the role
of the immune system during
pregnancy and the interactions
between the maternal immune
system and the placenta. Mor
analyzes studies related to
the immunology of implantation and provides a practical
approach for the application of
basic reproductive immunology
research to such pregnancy
complications as pre-eclampsia
and preterm labor.
The Profession of Ophthalmology: Practice Management,
Ethics and Advocacy
edited by David W. Parke II,
m.d., associate clinical professor
of ophthalmology and visual science (American Academy of
Ophthalmology). This three-part
volume contains blueprints for
business skills to develop and
manage successful practices; a
review of ophthalmology’s Code
of Ethics and real-life case studies illustrating ethical behavior
in ophthalmic-related situations;
and a discussion of the importance of advocating on behalf of
patients and the profession,
and principles and methods for
doing so.
“Shrink”: On Becoming
a Psychotherapist
by Louis B. Fierman, m.d., associate clinical professor of psychiatry (Blue Dolphin Publishing)
Fierman, now retired, recounts
his “only-in-America” journey
as the son of uneducated immigrant parents and how, with their
support, he pursued a career
as a maverick psychiatrist and
psychotherapist at Yale and
elsewhere.
14
books & ideas book notes
in circulation
Blogging saves doctors time
Travel and Tropical Medicine:
Infectious Disease Clinics of
North America
by Frank J. Bia, m.d., professor
of medicine and laboratory medicine, and David R. Hill, m.d.
(Saunders) Topics covered in this
guide include new vaccines
against yellow fever and Japanese encephalitis, the current
prevention of malaria and treatment of such common syndromes as traveler’s diarrhea
and cutaneous leishmaniasis.
Other chapters address pretravel screening of high-risk
travelers, problems associated
with airline travel, sexual
tourism and the interactions
between hiv infection and
tropical diseases.
Kelley’s Textbook on
Rheumatology, 7th ed.
by Clement B. Sledge, m.d. ’55,
Edward D. Harris Jr., m.d., Ralph
C. Budd, m.d., Gary S. Firestein,
m.d., Mark C. Genovese, m.d.,
John S. Sergent, m.d., and Shaun
Ruddy, m.d. (Saunders) This
book provides encyclopedic coverage not only of the etiology
and pathogenesis of rheumatic
diseases, but also of the biology
of the normal joint, immune
and inflammatory responses,
evaluation of the patient and
diagnostic tests and procedures.
The book includes a bound-in
dvd with chapter-by-chapter
multiple-choice questions for
board review.
Understanding Cancer:
A Patient’s Guide to Diagnosis,
Prognosis, and Treatment,
2nd ed.
by C. Norman Coleman, m.d. ’70
(Johns Hopkins University Press)
This book describes new treatments that target specific types
of cancer and explains how to
gather and interpret information
when making decisions about
treatments. It also provides
guidance for preparing for visits
to doctors and the hospital.
Topics include biomarkers, novel
imaging techniques, molecular
signatures and profiling and
molecular-targeted therapy.
Some of these therapies are currently available only through
clinical trials, and the author
includes a detailed discussion of
what is involved in participating in such trials.
The descriptions above are based on
information from the publishers.
send notices of new books to
Cheryl Violante, Yale Medicine,
New Haven, CT 06511, or via e-mail
to cheryl.violante@yale.edu
With all the information on the Web already, why would
anyone want to add to the volume by reading blogs? To save
time, according to librarians at Yale’s Cushing/Whitney
Medical Library.
Yale reference librarian Charles J. Greenberg, m.l.s., m.ed.,
for example, maintains a blog for surgeons at http://surgeryupdate.blogspot.com. “Surgeons don’t have time to look at
all the journals,” said Greenberg, the library’s coordinator
of curriculum and research support. He describes his blog
as “the equivalent of a newsstand for information on certain
emerging surgical topics.” Greenberg assembles his “newsstand” by combing 30 leading medical and surgical journals
each month and posting entries on surgical news two or
three times a week.
Greenberg’s blog can be reached from the home page of
the medical library, which maintains its own blog (http://
elibrary.med.yale.edu/blog/) to inform visitors of library
news. Postings include descriptions of two newly acquired
electronic databases offered by the library, one containing
1,800 online journals (The ScienceDirect Freedom Collection),
and the other listing drug eruptions and interactions.
The library website lists links to two other blogs by Yale
medical librarians. Education services librarian Jan Glover,
m.l.s., uses hers to dispense advice about doing online
research (http://janstips.blogspot.com/). Glover posts research
tips and entries that highlight databases. “Someone might
not know a database existed, and it might be perfect for their
topic,” she said.
Janene Batten, m.l.s., reference librarian for the School
of Nursing, started a blog about 18 months ago that focuses
on items of interest to nurses (http://ysnlibrary.blogspot.com/),
and she posts something new several times a week.
Blogging took off during the run-up to the 2004 general
election, said Web Services Librarian Hongbin Liu, m.l.s.,
who coordinates the library’s blogs. With blogs, said Liu,
“everybody can be a freelance journalist.” Liu uses Technorati,
a blog search engine, to monitor the growth of blogs. As
of October there were 56.4 million blogs worldwide, not
counting some of those that are written in languages other
than English. Blogging, says Liu, is here to stay.
—Cathy Shufro
In Circulation focuses on activities at the Cushing/Whitney Medical
Library. Send suggestions to Cathy Shufro at cathy.shufro@yale.edu.
15
on campus
A RT H U R C A P L A N
R O B E RTO J O H A N S S O N
KENNETH LUDMERER
R O B E RT S A P O L S K Y
Changing the ethical culture
of pharma
An ongoing disaster
stemming from neglect
Tracing the history
of medical education
Baboons, humans and stress:
the cost of being an sob
The last five years, said Arthur
Caplan, ph.d., have seen the
demonization of the pharmaceutical industry. Conflicts of interest, censored scientists, flawed
drugs and devices placed on the
market and the failure to protect subjects of clinical trials
have been “flat-out ethical disasters,” said Caplan, chair of
the Department of Medical Ethics
at the University of Pennsylvania School of Medicine.
Nevertheless, he told an
audience at the School of
Management in September, this
demonization is irresponsible.
“The pharmaceutical industry is
not the tobacco industry,” he
said. “The pharmaceutical industry produces medicines that
relieve pain, save lives and cure
patients. The pharmaceutical
industry does do a lot of good.”
How, he asked, can the industry change its ethical culture?
He called for mandatory registries of all clinical trials that
would make data—and reports
of adverse events—public.
Epidemiology, he said, must
trump marketing. He also called
for tougher Food and Drug
Administration monitoring of
Phase IV, when drugs are in
the marketplace.
“I think pharmaceuticals
need to commit to the scientific
foundations of the industry,”
he said.
—John Curtis
For Roberto Johansson, m.d.,
ph.d., Hurricane Katrina was a
disaster that didn’t have to
happen. During a talk at the
Department of Epidemiology
and Public Health in October,
he described what he saw in
his hometown of New Orleans.
“Roads were out. Telephone
lines were out. The fire department broke down. ems totally
broke down. The hospitals were
marginal at best,” he said.
But a long history of neglect—of the levees, of the city’s
schools and of the city’s poor—
compounded the problem, he
said. And the order to evacuate
came late. “Many of the people
who stayed couldn’t get out
because they were medically
disabled or poor,” he said, noting
that doctors, nurses and other
health care workers stayed on
their jobs.
Disasters, he said, follow five
stages. First comes knowledge
of a possible disaster, followed
by a warning phase. Then comes
impact. In the rescue phase
first responders try to save lives,
and those outside the strike
zone mobilize to help. The recovery phase, in which New Orleans
finds itself, tries to keep survivors
at a functioning level.
“Katrina,” he said, “is a story
that must not be forgotten.”
—J.C.
In the mid-19th century, medical
schools were faculty-owned, forprofit operations that churned
out doctors after just a few
months of lectures.
With the Flexner Report of
1910, medical educators realized
that medical schools should be
integral parts of universities,
said Kenneth M. Ludmerer, m.d.,
professor of medicine and history at Washington University in
St. Louis, in his address at the
30th Annual Yale Affiliated Hospitals Symposium in November.
By the 1920s, medical schools
had become academic centers
that emphasized research and
clinical care. The fee-for-service
era of the 1960s to 1980s also
afforded rich learning opportunities because hospital stays were
longer. But that learning environment has been threatened by
managed care, with its emphasis
on seeing as many patients as
possible.
Today, Ludmerer sees a need
for a social contract that funds
and values medical education
and research, while medical
schools teach and practice costeffective medicine. Despite the
faults of the current system,
Ludmerer said he wouldn’t trade
today’s problems for those of a
century ago. “It’s better to have
problems financing treatment
for Alzheimer’s disease and cancer than to watch children die
of diphtheria,” he said.
—Jill Max
Baboons in Africa’s Serengeti
Plain spend just three hours a
day finding food, said Robert
Sapolsky, ph.d. “That leaves nine
hours of daylight for them to
be really crappy to the other
baboons,” Sapolsky said, adding
that such behavior carries a cost.
“Physiologically, it’s very expensive to be a bastard all day long.”
In his keynote talk at a symposium in October sponsored by
the Department of Psychiatry,
Sapolsky, a professor of biological sciences and neurology and
neurological sciences at Stanford University, described how
chronic stress—in humans as
well as baboons—can cause or
contribute to physical and
mental afflictions ranging from
heart disease, ulcers and memory loss to infertility and even
diminished growth. “If stress
goes on too long, it becomes
pathogenic,” he said.
But Sapolsky, who studies
the relationship between
personality and stress-related
disease in wild baboons, found
cause for optimism. Male
baboons have “pungent individualistic personalities,” he said.
Some handle stress well; others
don’t. There is compelling
evidence that the same is true
for humans. “If some baboons
see the watering hole as half
full, so can we,” he said.
—Jennifer Kaylin
capsule
b o t t o m In the United States the Spanish
influenza pandemic of 1918 struck 28 percent of
the population, killing 675,000 and depressing
the average life span by 10 years. In Kansas,
Camp Funston, built during World War I as a
training camp, also served as an emergency
hospital during the epidemic.
Yale’s Army Medical Laboratory and
the 1918 Influenza Pandemic
Studies undertaken during World War I led to breakthroughs in chemotherapy,
providing a new understanding of the pathology of the deadly influenza virus.
By Jennifer Kaylin
b e l o w When Milton Winternitz came to
Yale as chair of pathology in 1917, he brought
with him a commitment to the U.S. Army to
study the poison gases being used in the war.
During the pandemic the Army Laboratory
School at Yale, which studied human pathology, autopsied flu victims in New Haven.
c u s h i n g / w h i t n e y m e d i c a l h i sto r i c a l l i b r a r y
16
The two facilities established at Yale
during World War I for training
lab technicians for fieldwork and for
studying the effects of poison gas were
in existence for only three years, but
during that brief period they created
a legacy of teaching and patient care
that is still relevant to students at
the School of Medicine and to health
practitioners around the world.
“In the early 20th century, Yale
wasn’t a leader. There was no full-time
faculty, and the teaching was mostly
rote memorization followed by an
apprenticeship,” said Michael Kashgarian, m.d. ’58, hs ’63, professor of
pathology and molecular, cellular and
developmental biology.
That changed in 1917, when Milton
C. Winternitz, m.d., became chair of
Yale’s Department of Pathology. Winternitz brought with him the conviction
that the study of medicine needed
to be supported by science. He also
brought a commitment to the U.S. Army
that he would investigate the pathology of the poison gases that were being
used in the Great War.
The Army set up the Medical Division of the Chemical Warfare Service at
Yale and the Army Laboratory School
at Yale, both to be overseen by Winternitz. The first facility focused on experimental animal pathology. Using dogs
as experimental subjects, researchers
counted red and white blood cells and
examined the organs after the dogs
were repeatedly exposed to poison gases.
They described how these chemicals
kill cells, and they made the significant
observation that nitrogen mustard is
particularly lethal to lymphoid tissues.
Researchers at the second facility concentrated on human pathology, examining in autopsy the lungs of patients
who had been exposed to mustard gas.
Together, the two facilities provided the
ideal setting for Winternitz to introduce
his new scientifically based pedagogy.
In the midst of their work on gases
used in war, researchers were hit with a
new challenge: the influenza pandemic.
In the autumn of 1918, this acute respi-
ratory infection made its first appearance on the New England coast.
“Terrible as has been the war, the
cost of life and distress … has been
infinitesimal compared to the havoc
caused by the late epidemic of influenza,” reads a passage from the New
Haven Health Department’s 1918
annual report. From October through
December of that year, the department
recorded 777 deaths from influenza
and its complications.
“People were healthy in the morning and dead by nightfall,” said Martin
E. Gordon, m.d. ’46, clinical professor
of medicine and chair of the board
of trustees of the Cushing/Whitney
Medical Library Associates.
The Army Laboratory School at Yale,
located in the Brady Laboratory and
one of several such schools around the
country, was also set up to train laboratory technicians in bacteriology and
pathology before dispatching them to
medical field units. After the flu outbreak, the Laboratory School assumed
the task of performing autopsies of the
victims. They found that the pathology
produced by influenza pneumonia
closely resembled that produced by the
inhalation of certain types of poison
gas. Illustrators made a series of watercolors and drawings of the characteristic lesions. These pictures were part of
an exhibit produced by Gordon called
“The Flu and You:Old and New Threats”
that appeared in conjunction with a
lecture last spring by Harvey Fineberg,
m.d., president of the Institute of
Medicine of the National Academies
of Science.
The work of both the poison gas
and influenza researchers is also
preserved in three monographs: The
Pathology of War Gas Poisoning, Lethal
War Gases—Physiology and Experimental
Treatment and Pathology of Influenza.
By the standards of the time, Kashgarian
said, the biochemical and pathological
observations presented in these volumes were state of the art, but even
by today’s standards, they provide a
“strong basis” for additional studies.
“Given the tools they had, the information they present is very complete
and thorough,” said Kashgarian.
One observation stands out—the
researchers noticed that lymphatic
and bone marrow tissue are destroyed
by mustard gas. The therapeutic
potential of this observation wasn’t
explored until years later, but eventually researchers found that nitrogen
mustard, derived from the family
of chemicals used in battle, caused
tumors in mice to shrink. Human
trials were equally encouraging and
paved the way for treating cancer
with chemicals.
Jennifer Kaylin is a contributing editor of Yale
Medicine and a freelance writer in New Haven.
armin hemberger
n at i o n a l m u s e u m o f h e a lt h a n d m e d i c i n e
17
Studies of the pathology of the 1918 influenza
pandemic in New Haven yielded three publications, and illustrations of diseased tissue by
Armin Hemberger. His images appeared in Experimental Treatment and Pathology of Influenza,
which counted Winternitz as one of its authors.
steps 1–3 are executed only once
18
transposase gene
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transposon
RFP
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▲
FROM A MOTH, A TOOL TO DECODE GENE FUNCTION IN MAMMALS
Transposons are snippets of dna that are also known as jumping genes because they move around a genome.
Their movements are random, but they typically insert themselves into other genes and disrupt their
functions, causing a mutation. For more than 50 years scientists have been looking for a transposon that can
efficiently work in mammals. Tian Xu has modified a transposon from the cabbage looper moth and uses
this transposon system to mutate genes in mice and discover their functions. The process is described below.
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The piggyBac transposon, found in
the cabbage looper moth, is split
into two modified dna plasmids.
One, the transposon lacking the
gene that expresses the jumping
enzyme transposase, carries a red
fluorescent protein (rfp) marker.
The other is the modified transposase gene, plus a gene that causes
a mouse’s coat to turn black.
Each plasmid is injected into a
different mouse embryo. As
the mice grow, their appearance
reflects their genetic status—
mice that carry the transposon
gene glow pink under ultraviolet
light; black mice carry transposase,
the jumping enzyme. A black
mouse and pink mouse are bred.
Some of their offspring—identified
by a black coat and a pink glow—
carry both the transposon and
transposase and have actively
jumping genes.
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recycled for breeding
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These mice are bred with normal
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19
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How fruit fly geneticist Tian Xu is transforming the mouse into
a genetics workhorse to reveal the causes of human disease.
Story begins on page 20
5
6
7
8
Some of their offspring will inherit
a mutation but not the jumping
enzyme. Without the enzyme, the
transposon remains in place, and
polymerase chain reaction will
reveal which gene has been disrupted. Other offspring will inherit
both the mutation and the jumping enzyme and can be bred with
normal mice, as in step 4, to produce mice with different mutations.
Mutant mice are bred with normal
mice to produce offspring that
have the same stable mutation.
Mice, each carrying one copy of
the same mutation, are bred. The
breeding of these two heterozygous mice will produce a homozygous mouse with identical
copies of the same gene mutation.
The offspring with two copies of the
same mutation can be identified by
a red glow because they also carry
two copies of the rfp gene. If a defect
results, researchers can discern the
function of that gene by the consequences of the mutation. Xu’s goal
is to determine the cause of singlegene diseases by doing this type of
analysis for each of the 20,000 mouse
genes that have not been analyzed.
i l l u st r at i o n s b y e m i ly d a m st r a / d i a g r a m b y d a p h n e g e i s m a r
20
by Pat McCaffrey
Sitting in a standard-issue clear plastic cage among hundreds
of other white laboratory mice, the piggyBac mouse looks
absolutely ordinary, not a bit like an animal poised to turn
human genetics research on its head. But when Tian Xu,
ph.d., professor of genetics, switches on an ultraviolet lamp,
the mouse emits a faint pink glow—an aura that holds the
secret of its transformative power. If Xu, professor and vice
chair of genetics and the mouse’s inventor, has his way, he
will breed up to a million more pink animals. Those animals, he says, will reveal the causes—and in some cases the
cures—for myriad human diseases.
What is piggyBac’s secret? Xu knows, because he engineered the mouse to carry a small piece of moth dna,
a “jumping gene” called the piggyBac transposon, which in
turn carries a genetic marker to turn the mouse pink for easy
identification. The jumping gene makes the mouse a mutant
factory: when the animal breeds, the transposon causes
random genetic mutations in the mouse’s offspring—one
gene per mouse is disabled. Compared to current methods
for making experimental mice, known as knockouts, using
piggyBac is 100 times quicker and cheaper.
Xu eventually plans to produce 100,000 new strains of
mice with missing genes. Among them, he expects to find a
knockout for the majority of the estimated 25,000 to 30,000
genes in the mouse genome. More than 99 percent of mouse
genes have direct equivalents in humans, and so these mice
will provide the first glimpse of the functions of many of our
genes, most of which remain mysterious half a decade after
the human genome project first cataloged their existence.
terry dagradi
From China to Yale
Tian Xu has found a method of
making knockout mice that is
faster and far less expensive than
conventional technology.
Tian Xu came to New York City from China in 1983, a 21-yearold refugee from the Cultural Revolution pursuing graduate
work in genetics at City College. After six months of living on
a partial teaching assistant’s stipend in an abandoned building in Harlem, he received an offer he couldn’t refuse: a full
scholarship to Yale. He was soon in New Haven, studying the
development of the fruit fly Drosophila melanogaster with cell
biologist Spyros Artavanis-Tsakonas, ph.d.
His good fortune did not impress his mother in China.
“It was the first time she’d heard from me in six
months, because I couldn’t afford to call home. But this was
big news.” When Xu’s mom asked what he intended to
study, Xu replied, “I’m gonna work on flies, Mom.” After a
very long silence, his mother spoke: “Son, we have a lot of
flies right here in our hometown.”
21
For a geneticist, fruit flies are a model organism for
figuring out what genes, and the proteins they encode, actually do. The ability to produce hundreds, even thousands,
of mutant flies quickly by using chemicals, radiation or even
transposons lets researchers look for traits they are interested in, such as slow growth or crippled wings.
This kind of large-scale mutagenic analysis, called
a forward genetic screen, has been a staple of fly research
for decades. And at his lab in Yale’s genetics department
Xu has used the technique to unravel the biochemical
pathways involved in cancer cell growth and metastasis
in Drosophila.
Forward genetic screens have played a pivotal role in
our understanding of modern biology in lower organisms,
including bacteria, yeast, flies, worms, plants and zebrafish.
But the lack of comparable genetic screens in mammals has
impaired our ability to understand many aspects of human
biology and disease. Xu felt that his fly work could only
begin to approximate human disease because of the wide
evolutionary distance between the two organisms. Moving
his research closer to humans meant moving to the mouse.
Are you a mouse or a man?
Like humans, mice are mammals, with similar anatomy,
physiology and developmental stages. They breed rapidly
and can be inbred to produce large numbers of identical animals. Their care and feeding are more complicated and
costly than that required for fruit flies, but as higher animals
go, they are small and inexpensive.
For years, the obstacle to genetic studies in mice
was a lack of tools for mutating genes en masse for forward
genetic screening. Starting in 1981 with Frank H. Ruddle,
ph.d., Sterling Professor of Molecular, Cellular and Developmental Biology at Yale, researchers developed genetic engineering methods that allowed them to add and subtract
genes from mice, and these methods revolutionized the use
of mice for targeted genetic research.
Today, researchers can selectively mutate mouse genes
at will. Typically, they use genetically altered embryonic stem
cells to create embryos, which mature and pass the altered
genes on to their offspring. The process is investigatordriven—scientists decide which genes to add or eliminate.
From choosing a gene and designing a piece of dna to disrupt it, to creating embryonic stem cells and injecting the
cells into embryos to produce mice, to breeding out the final
mutants, each new knockout is a custom product that takes
a year and approximately $100,000 to bring to life. But
the goal of large-scale systematic mutations in the mouse
genome has remained elusive. Efforts to use chemical
mutagens or viruses to disrupt large numbers of genes have
been abandoned as too expensive and unpredictable.
Xu had a different idea. He wanted to create mutant
mice as easily as he had made mutant fruit flies. He didn’t
want one or two or even 10 mouse mutants—he wanted a
complete collection, one mouse strain for each gene, that
would allow him and scientists around the world to discover
the roles of genes in human disease. “I thought if we could
do the kind of work in mammals that we do in flies, that
would be tremendous.”
For that, he needed a new tool.
Finding piggyBac
Based on his experience with Drosophila, Xu believed a
transposon could do the trick for wide-scale mutagenesis in
mice. Transposons, also known as jumping genes, were
first described in corn in the 1950s by Barbara McClintock,
ph.d., who won the 1983 Nobel Prize in physiology or
medicine for her discovery that the varied colors of Indian
corn kernels arise from the disruption of pigmentation
genes by transposons.
Mere snippets of genetic material, transposons insert
themselves at random in the middle of the long dna molecules that make up chromosomes. If they happen to land in
the middle of a gene, the sequence becomes hopelessly garbled and the gene becomes nonfunctional. Over the course
of evolution, transposons have remained active in plants and
insects, presumably because they generate genetic diversity.
For reasons that aren’t entirely understood, the abundant
transposons in mammalian genomes (they make up as much
as 40 percent of human dna) have been “disabled,” perhaps to protect organisms from unwanted mutations.
Despite decades of efforts by many researchers, no one had
succeeded in discovering or engineering an efficient transposon in mammals.
Xu imagined using transposons like buckshot to
pepper the mouse genome, where they would randomly
insert themselves into genes and generate large numbers
of mice with uniquely altered outward characteristics, or
phenotypes. “People said I was crazy,” Xu recalls. “They
said, you’ve never trained in mouse genetics. You’ve never
even touched a mouse.”
Xu didn’t give up his day job; he kept his lab pushing
ahead with its regular Drosophila work. On the side, though,
he continued to search for the elusive transposon. In 1996
22
he applied for funding from the Howard Hughes Medical
Institute, a foundation known for supporting risky but
promising ventures. With its support, over the last eight
years he has tested a succession of transposons and viruses
from plants, insects and wherever he could find them.
Finally, he tried a strange-looking transposon known
as piggyBac, found in the cabbage looper moth. It was different from anything else he had seen, and it was so exotic
Xu figured it might work. PiggyBac had been discovered
several years earlier by Malcolm Fraser, ph.d., at the University of Notre Dame in Indiana, and it had already been
shown to suppress gene activity in insects.
After engineering the piggyBac transposon to adapt
it for mammalian cells, Xu found that it worked, and Xu’s
mutant mice were featured on the cover of the journal Cell
on August 12, 2005. “We don’t know why this one works
while others don’t,” Xu said at the time, “It just works. We
have a magical tool now.” Xu and colleagues further engineered a red fluorescent protein gene from jellyfish, which
they added to the transposon, allowing them to identify visually which mouse carries a mutation and which is a mutant.
Mutants-R-Us
With quick and easy generation and recognition of mutants,
the mammalian piggyBac transposon system is ideal for the
large-scale project Xu envisioned. Besting the standard time
requirement of one year per mutant mouse, within months
the researchers had created 460 unique mutant mice.
Among the first batch of 95 mutants they examined
in depth were mice with tusks, mice with neurodegeneration, mice that could not sense pain, mice that turn only
leftward, mice that don’t grow and mice with bad manners.
Then there were the sterile mice, and mice never even
born because their defects were lethal early in development.
In each case, these afflicted mice will lead the researchers
to single genes critical for growth and development, autoimmune disease, social behavior, spinal cord defects and
neurodegeneration.
“This is only looking at the first 95—imagine if we
mutate every gene and look through them all, what we will
find,” Xu says. The hit-or-miss nature of piggyBac mutations
gives researchers a decided advantage over knockouts produced using embryonic stem (ES) cells, he says. PiggyBac
allows scientists to study genes they didn’t even know existed.
“We don’t pick which genes to get rid of. We just make the
mutants randomly and let the animals tell us which ones
are important. This is a critical difference, because scientists
are not that smart that they always pick the right gene to
knock out.”
Richard P. Lifton, m.d., ph.d., chair and Sterling
Professor of Genetics, an expert on hypertension genes and
a Howard Hughes Medical Institute investigator, agrees.
Lifton says, “That’s the power of forward genetic screens.
They allow us to find genes that affect these phenotypes that
up to now we’ve had no idea about at all.”
So unlike the ES cell method, which focuses exclusively on known genes, the unbiased approach of transposonbased mutagenesis can open up exploration of the entire
genome, including areas of the genome previously dismissed
as “junk” dna.
Time for a new mouse
Xu’s development of the piggyBac mouse came as the drawbacks of the knockout technique were holding back mouse
genetics, despite international support for a centralized
program to knock out every gene in the mouse. First, the
process of producing knockout mice via ES cell engineering
is slow and expensive. According to the National Institutes
of Health (nih), about 11,000 mouse knockouts have been
generated since the late 1980s, but that number is less
impressive than it seems. Many genes have been knocked
out more than once by different labs—one gene was
knocked out independently at least 28 times. Of the estimated 25,000 mouse genes, only about 4,000 have been
published, and studies of those genes have been limited
to specific areas.
And not all mouse mutants are available to all
researchers. Given the time and resources invested in making knockouts, some researchers want to keep their own
mice close to home, impeding the sharing of reagents and
increasing the chances for redundancy and waste.
To solve some of these shortcomings, the nih has set
aside $50 million to establish a central repository for 10,000
mutant ES cell lines. The lines, which will be produced over
the next five years, will be freely available to all researchers,
who can request the ES cells and then use them to produce
their own knockout mice in their labs. A parallel effort,
using different strains of mice and creating a different type
of knockout, is being started by an international consortium
that includes Canada and several European countries.
Xu thinks that the key is to produce mutant animals
that will reveal defects and diseases. Producing mutant
animals from ES cells is a long process. The piggyBac mouse
system can reach the goal faster and cheaper because it
produces mutant animals in a highly efficient and costeffective fashion, and allows rapid identification of mutants
for analysis. His plan is to produce up to 100,000 mutant
strains, each of which carries a single transposon mapped
to a known site. A bank of frozen piggyBac mutant embryos
would then be generated for distribution to researchers
around the world. The resource would enable researchers in
all fields of medicine to study the genes regulating the disorders they encounter, Xu says.
Going with piggyBac for genome-wide mutagenesis
has other advantages, too. Transposons may be the only way
to generate mutants in dozens of strains of mice for which
23
ES cell cultures are not available. There are more than 200
breeds of mice used by researchers, each with its own personality. Some are preferred by immunologists, while others
are better for neurological studies. To move a mutation
between strains takes two or three years, which might be
skipped altogether by utilizing transposon technology.
Transposons could theoretically be used in other species, too,
like the rat.
From Yale back to China
To produce the million mice it will take to find 100,000
mutants, Xu and the School of Medicine have embarked on
a joint research project with his alma mater, Fudan University
in Shanghai. The mutagenesis of the mice will be done at
Fudan, where Xu and his colleagues have set up a state-ofthe-art mouse facility and production lab supported by
Chinese government funds. Researchers in China have produced the first 500 mutants already, including the 460
Xu’s team produced. But finishing the job will require much
more funding, and Xu is on the stump for that now.
He has applied for nih funding for the research at
Fudan, to produce 500 more mouse mutants in a pilot
project. Xu wants to demonstrate that piggyBac can work in
a different strain of mouse, and specifically in the strain
that was selected for the nih ES cell-based knockout project.
One way or another, the mutants will all be made within
five years, according to Xu. “We hope that our project will
be supported by the nih so that the mutants will be available to the scientific community throughout the world as
soon as possible.”
Making the mutants is just the first step of Xu’s plan,
and not even the most ambitious part. Once the mutants
are created, the real work begins. Every one of the million
mutant mice will need a thorough physical exam. The project, which Xu envisions carrying out at Yale, calls for a full
workup for each mouse, and could include a CT scan, blood
work and measures of immune, kidney, lung and cardiovascular function, as well as of behavior. Not all the mice will
appear sick—many will seem perfectly normal until
researchers take a closer look.
“Now, researchers generate their own mutant mice
and study only the processes they are interested in,” Xu
explains. “For example, they make one or a few mutations
and look for hypertension. If they see hypertension, that’s
great. But if they do not see hypertension, that’s the end
of the story, and they will most likely abandon the mice.
But those mice could easily have diabetes, a very significant
piece of information that would be totally missed. Furthermore, researchers working on different diseases and biological processes are now repeatedly mutating the same genes
in ES cells and/or taking the same ES cell line to repeatedly
produce the same mutant mice. There is a significant waste
of resources.”
The centralized and comprehensive phenotyping will
allow researchers to choose only the genes of interest for indepth mechanistic studies and ensures that the mice rapidly
make their way into the labs of experts who can best utilize
them to discover new treatments for disease. Right now,
Yale scientists are defining a scientifically solid and practical
panel of phenotyping procedures that will cover the widest
possible range of diseases.
They believe their integrated approach will provide the
biggest return on the piggyBac investment. They plan to make
their results—and their mice—freely available to researchers
all over the world. Xu wants to see all data posted on the
Web, where interested scientists can troll for new genes for
their favorite disease, then order off-the-shelf mice for
their experiments.
Besides having an impact on the most common major
diseases, the mouse studies will advance research into orphan
diseases—neglected conditions affecting so few people that
they do not attract interest from for-profit drug companies.
“There are about 6,000 orphan diseases. While each one
affects only a small part of the population, all together they
affect many people. We have a solution to the problem of
lack of interest, because by the process of systematically
mutating every gene and screening through our mice, we
will identify many of the genes that are responsible for
these diseases,” says Xu.
Ultimately, Xu hopes to create more than just mice.
“I want to make Yale the premier international center
for human disease studies. The aim is to set up a center,
based on these mice, which will attract researchers from all
over the world. Each one can focus on a disease, and identify
the causes of that disease right here. Then, they will move
on to develop a career studying the mechanism of each disease and finding a cure,” Xu says. “When I came to the
United States 23 years ago, I had $50 to my name. Yale gave
me a research fellowship and changed my life. Now, we have
a chance with these mice to cultivate a new generation of
physician-scientists, who will mushroom out to solve disease
and help millions of patients. That would really be my
dream come true.” YM
Pat McCaffrey is a freelance writer in Boston.
24
25
a letter from niger
Water is life
The 500,000 inhabitants of the Azawak plains of Niger wage a daily
struggle to find enough water for their basic needs. Through her
photographs, an alumna of epidemiology and public health hopes to
draw attention to their plight and improve their lives.
Text and photographs by Ariane Kirtley, m.p.h. ’04
In the Tuareg camp of Tchintaloukan,
18-year-old Againakou gives her 10month-old son, Agoubouley, a drink
of marsh water. Such water can be
deadly—10 of 120 children in another
camp visited by author Ariane Kirtley
died of diarrheal diseases caused by
drinking the water.
26
Water is life
W
hen I threw a pebble into Mohammed and Gonda’s
well, I heard a faint thump, not the splashing of water. “How
deep is it?” I asked. Two hundred feet, I was told, and no
sign of water.
For six years Mohammed and Gonda’s families from
neighboring villages and camps in the Azawak plains of
the Republic of Niger pooled their resources to dig an adobe
well. Then they abandoned their efforts. There was no more
money to dig deeper or to line the well with cement—the
adobe well threatened to cave in. Even if the families had had
the resources, it would take six more years to reach water. In
the Azawak the first water table typically lies 430 feet underground, and renewable aquifers are at 700 to 1,400 feet.
Because the people of the Azawak cannot afford pumps and
pipes, there are few sources of water, and none are permanent or reliable because they dry up from overuse.
Finding water occupies the lives of the 500,000 members of the Tuareg and Woodabe Fulani ethnic groups who
make their homes in the plains’ 200,000 square kilometers.
Most of the year there is no water. During the rainy season
from July through September, the pastures turn green, the
animals grow fat, milk is plentiful and water overflows from
marshes that reappear after nine months of drought. The
water, fouled by animal and human waste, may be darker
than coffee and dirtier than a New York City mud puddle,
but people drink and bathe to their hearts’ content. Dysentery
and diarrhea soon follow.
While in the Azawak, Kirtley stayed
with families in their homesteads,
camps and villages. In January
2006, during a Muslim festival, she
posed with children of Tantigellay
Teckniwen, a Tuareg camp.
Most of the inhabitants of Niger’s
Azawak plains belong to the Tuareg
and Fulani ethnic groups. Pastoralists, they graze livestock, driving
them as far as 350 miles in search
of water. Author Ariane Kirtley
describes the region as a “rich and
diverse land of extremes: extreme
kindness, extreme heat, extreme
beauty and extreme challenges.”
When the marshes dry up, people travel by foot or
donkey to find water. Prevented by local populations from
settling near the few sources of water that exist on the outskirts of the territory, they repeat their search every day.
The men travel up to 350 miles south seeking water for their
livestock, and the search for water becomes a daily chore
for women and children. Children as young as 9 or 10 may
travel—with temperatures topping 100 degrees—10 to 17
miles to the nearest well, only to wait for hours for their turn
to fetch water. Often their turn comes too late, as the other
people and their livestock sharing the well have left it dry.
The children may stay at the marsh as long as three days
while the water is replenished.
Water consumption in these plains, less than a gallon
and a half per person per day, is well below the World Health
Organization’s recommendation of 6.5 gallons. During the dry
season, water is reserved for drinking and cooking—personal
washing awaits the return of the rains. In the Azawak almost
half the children die before their fifth birthday.
Despite the hardships, people stay in the Azawak. It is
their traditional home, but on a practical level, they have no
place to go. Their numbers are too large for relocation, and
moving elsewhere could lead to strife with other ethnic groups.
Finding water
Although I spent the first 10 years of my life in Africa, I had
never seen an area as poor as the Azawak. With my brother
27
and our National Geographic journalist parents, I lived among
the nomadic Bozo fishermen in Mali, the Ibadite Muslims of
central Algeria, the animist Gueré “panther men” of western
Ivory Coast and the Inadan Tuareg artisans of Niger’s Aïr
Mountains in the Sahara Desert.
I studied public health at Yale and for my internship
returned to Niger to work on a hygiene and sanitation program with care. After graduating in 2004, I went back to
Niger as a Fulbright Scholar to build upon my work with
care. My Fulbright research revealed significant variations
in knowledge, attitudes, behaviors and resources relating to
health and nutrition among seven ethnic groups living in
rural Niger. (For example, of 700 men I interviewed in the
Azawak, only three had heard of aids, and all three believed
it resulted from women having sex with dogs.) With this
information I created a database that allows health organizations to tailor their programs to their target populations’
unique needs and attributes.
During my Fulbright research I discovered the Azawak.
My research assistant, Moustapha, whose family had abandoned the plains during the drought of 1974, persuaded
me to visit his homeland. Little did I know that my visit in
September 2005, which was to last only a month, would
consume me professionally ever since. I spent October
and November 2005 attempting to interest humanitarian
organizations in the Azawak. With a team of Nigerien
employees from a large international humanitarian agency,
we wrote a proposal to fund a water and food program. It
was rejected because the Azawak is “too vast and remote”—
the organization did not want to risk its employees in a
region without water.
Realizing that I had to take the first step if humanitarian aid is to reach the Azawak, I have founded Amman
Imman, which means “water is life” in Tamachek, the
Tuareg language. Amman Imman has been raising money
since February 2006, with a goal of $280,000 for a pilot
program to build two borehole wells, each of which could
provide water for 25,000 people. With more funding, we
hope to sink even more such wells. Once water is available,
humanitarian organizations may safely send workers to
improve the lives of one of the most vulnerable populations
on earth. (More information about the project is available
at www.waterforniger.org.)
The people of the Azawak
Most people of the Azawak are pastoral nomads of the
Tuareg and Woodabe Fulani ethnic groups. The Tuaregs of
the Azawak have retained a nomadic existence, herding
cattle, camels, goats and sheep, and living in tents of reddyed goat hide in camps of 50 to 150 people. During the
rainy season, they move every three to four days in search
of pastures. In the dry season they move often within
their “home territories,” land occupied by their families
for generations.
Gonda and Mohammed spent
six years trying to dig a well, with
money raised from their Tuareg
families and neighbors. They abandoned their efforts over a lack
of money and worries that the
well would collapse.
28
Water is life
Throughout her travels in the
Azawak, Kirtley captured images
of daily life and portraits of the
Woodabe and Tuareg peoples.
The Woodabe are nomadic cattle herders who live in
camps of one or two families and move frequently to greener
pastures. Their homesteads consist of a traditional wooden
bed (covered with a plastic sheet when threatened by rain or
sun) and a wooden table covered with 20 to 30 calabashes—
bottle gourds hollowed out and dried for use as containers.
Only a few of these calabashes hold grain or milk—the rest
are on display as a sign of the woman’s wealth.
Sedentary villages grow more common as drought
takes its toll on livestock. Without animals for their livelihood, the nomads settle into villages of between 100 and
300 people and try to survive through subsistence agriculture, mostly growing millet and sorghum. But even they
abandon their villages to search for water during the harshest months of the dry season.
Hospitality and hope
Sadouan was the first to greet me as my research assistant,
Moustapha, and I arrived at our Tuareg host camp in September 2005. She invited me to her tent, prepared a traditional bed of large wooden poles and woven mats, and gave
me a mosquito net and elaborate leather pillows for armrests.
Late into the night her relatives came bearing bowls of
camel milk. Sitting on a pillow and sipping the frothy liquid,
with Moustapha as my interpreter, I had a conversation with
Sadouan’s husband, Alhassan. The camp and its herds, he
said, had recently returned from salt licks in the north. He
r i g h t Tackawel, a Tuareg woman
o p p o s i t e l e f t T he Woodabe,
who lives in a sedentary village
called Intatolen, pounded grain in
September 2005. Many inhabitants of the Azawak are turning to
raising grain instead of livestock
in order to feed their families.
a subgroup of the Fulani ethnic
group, move their camps of one or
two families every two or three
days. Their homesteads include a
wooden bed, which they cover
with a plastic sheet when it rains
or the sun is too harsh.
fa r r i g h t Muddy marsh water
is all that’s available for drinking,
bathing, cleaning and washing
dishes. In September 2005 in Tantigellay Teckniwen, a Tuareg woman,
Zeinabou, washed her bowls.
o p p o s i t e r i g h t In the region
of Inagar in January 2005, a
Woodabe Fulani family moved
camp with their belongings
carried on donkeys.
lamented losing 80 percent of his herd to drought that year.
“Around 100 of my camels died because they didn’t have
enough food and water. When we ourselves had no more food,
we also had to eat some of them. I sold others to buy millet for
Sadouan and the kids,” he said. “Ten years ago, only the poorest families in our camp owned fewer than 300 animals. With
only 20 animals left, what can I count on to survive? Maybe
if I grow enough millet this year, we’ll have enough to eat.”
After putting her children to bed, Sadouan gently ran
her fingers through my hair. “Why haven’t you braided your
hair?” she asked, implying that she would never leave her
hair uncovered and unbraided. “If you want, I can wash it
with ochre, and give you the festivity braids.”
A wild harvest to fill empty bellies
The sun was setting as I arrived in the Tuareg village of
Intatolen to greetings from men and women returning from
a day planting millet. Two women waved me over to their
thatched hut to share their supper of wild squash and a
grain I didn’t recognize. After several minutes of silence,
I introduced myself and asked their names. They giggled.
I had committed senti by speaking while eating. A faux
pas in Tuareg tradition, senti is nonetheless covertly appreciated as a sign that the food was so good that it made your
mind wander from matters of etiquette.
“We would have liked to serve you meat, but all our
animals have died,” said Issibit, the elder of the two co-
29
wives, after dinner. “We ran out of rice a few weeks ago, and
so now we are eating wild grains until they too run out.
And the lacada, we are very embarrassed to have served you
the wild zucchini, but we have nothing else to eat.”
I later learned that eating wild grains and vegetables
is a sign of famine—they are eaten only when every other
food source has run out. My research revealed that 71 percent of the households that I interviewed went from eating
one or two meals a day supplemented with milk to one or
no meals a day, sometimes supplemented with far less milk.
And 91 percent reported resorting to eating wild grains,
squash and bitter berries.
From school to Guerwuls
Fada, about 14, adorned with charm talismans, a round feathertopped hat and a Tuareg saber, came bouncing toward me
as I struggled through prickly burrs. “Hey, follow me, I’ll show
you where it’s best to step,” he said. “Come to my camp. It’s
just over that dune.” Two hours and about 2,000 prickly burrs
later, with a herd of long-horned cows following, we arrived at
his home: a wooden bed and a table covered with calabashes.
The camp was deserted. “Oh, I forgot—everyone has
left to prepare for the Guerwul tomorrow.” I had heard of
Guerwuls, beauty competitions held by the Woodabe people,
a subgroup of the Fulani. “Can you come?” Fada asked.
I asked Fada about life as a herder. Had he ever been
to school? At first he laughed and then answered that the
Fulani reject formal education because they believe that
schools steal their children away from their pastoral lifestyle.
A child who attends school is considered dead because he or
she no longer understands magic or the art of herding.
This is how Fada’s uncle, Ali, came to go to school 35
years ago. French colonists demanded that his grandfather,
the chief of his camp, send the children to school in Tchintabaradène, the capital of the Azawak. He sent only his own
grandchildren to their “death,” Ali among them. Ali ran away
and hid in the bush for three weeks, traveling by foot through
unknown prairies. When he reached his camp, the white men
were waiting. He ran away five more times before accepting
his fate. Ali never returned to life as a herder. Instead, he traveled to Morocco and France to obtain a degree in sustainable
agriculture. Ali now works on crop productivity projects for a
nonprofit organization in southern Niger.
After I refreshed myself with a bowl of curdled cow
milk and promised to see Fada at the Guerwul, he said,
“I’d like to go to school someday and become like my Uncle
Ali. Maybe when I have children, there will be schools in
the Azawak for them to attend.” YM
Ariane Kirtley, m.p.h. ’04, grew up in Africa and has founded the nonprofit
organization Amman Imman to build permanent water sources in the
Azawak region of Niger.
30
31
Infectious disease,
internal medicine and
Paul Beeson
During his 13 years as chair, Paul Beeson made
internal medicine at Yale one of the best departments in the country. He is remembered for his
skill in the laboratory, his compassion for patients
and his nurturing of students and residents.
c u s h i n g / w h i t n e y m e d i c a l h i sto r i c a l l i b r a r y
by Richard Rapport, m.d.
Paul B. Beeson, m.d., former chair of internal medicine at Yale
and an internationally renowned physician and scientist, died
on August 14 in Exeter, N.H., at the age of 97.
Beeson held leadership posts at major academic medical centers, was an editor of two major textbooks on internal
medicine, advanced the study of fever and infection and was
a member of the National Academy of Sciences. Among the
honors he received was the Kober Medal, the highest award
given by the Association of American Physicians. In 1973, Queen
Elizabeth II named him an Honorary Knight Commander of
the Most Excellent Order of the British Empire, a rare honor
for an American, in recognition of his service as the Nuffield
Professor of Medicine at Oxford University.
While at Yale Beeson conducted groundbreaking research,
transformed the Department of Internal Medicine into a
national model and cemented his own reputation in medicine.
“When he came it was a relatively small department,” recalled
Arthur Ebbert Jr., m.d., professor emeritus of medicine, who was
hired by Beeson as an instructor in 1953. “He apparently had a
mandate to expand the department and to encourage patient
referrals from around the state. Before he came and reorganized
the department, if doctors had a patient they wanted advice
on, the patient went to New York or Boston.”
Beeson the scientist was the first to identify proteins
in white blood cells now recognized as cytokines, signaling
compounds used for intercellular communications, that also
Paul Beeson was widely regarded
as a scientist and a caring
physician, teacher and mentor.
play a role in the body’s response to infections. With one of
his residents, Robert G. Petersdorf, m.d. ’52, hs ’58, Beeson
subsequently wrote a paper on patients with persistent fevers
of 101 degrees or more. Published in the journal Medicine in
1961, the article is considered a “landmark,” said Lawrence S.
Cohen, m.d., hs ’65, the Ebenezer K. Hunt Professor of Medicine
and Special Advisor to the Dean. Cohen, an intern and resident
under Beeson, told The New York Times that the paper is “as
relevant in 2006 as in 1961, in pointing out causes that were
not obvious and teaching clinicians what they should be
thinking about in making a differential diagnosis.”
Beeson grew up in Anchorage, Alaska, where his father,
John Beeson, m.d., was a general practitioner and surgeon for
the Alaskan Railway. When he was 19, Paul Beeson followed
his older brother to McGill University, where both received
their medical degrees. After an internship at the University of
Pennsylvania, Beeson joined his father and brother in practice
in Ohio. The lure of research drew him to Rockefeller University,
and he subsequently took appointments at some of the most
prestigious academic and medical centers in the country.
He came to Yale in 1952 from Emory University. When
he left New Haven 13 years later to become the Nuffield
Professor of Medicine at Oxford, internal medicine at Yale
was regarded as the premier department in the country.
In 1981, the Paul B. Beeson Professorship in Internal Medicine
was established at Yale, endowed by a former colleague,
32
Infectious disease, internal medicine and Paul Beeson
Elisha Atkins, m.d., and his wife, Elizabeth. In 1996, the School
of Medicine named its medical service in Beeson’s honor.
In this article adapted from Physician: The Life of Paul
Beeson (Barricade Books, 2001), author Richard Rapport, m.d.,
describes Beeson’s tenure at Yale.
Beeson sat behind a glass-topped desk, rolling a letter opener
around in his fingers, while the patients admitted during
the night were presented to him by the residents. Laboratory
tests had become more sophisticated since Beeson’s own
house officer days, but history and physical examination
remained central to the process of diagnosis. The impact
of technological innovation was slight, in spite of cardiac
catheterization and even early angiography. Laboratory
values, X-ray results and physical examination were expected
to be reported efficiently by the sleep-deprived residents.
Long-windedness was abbreviated by an impatient tapping
of the letter opener. The house staff soon learned that,
while their new chair didn’t like mistakes, he tolerated them
as a function of learning. What he could not tolerate was
thoughtlessness. When it was uncovered that a patient had
been treated unkindly or misused, as happened the day
a resident referred to a homeless, alcoholic patient as “a 35year-old bum,” the letter opener snapped unhappily to the
desk and the room quieted while the offending resident
searched in vain for an escape. This happened rarely, a
testimony to both residents and chief, but when it did occur
it was remembered for the life of the perpetrator.
Teaching on the wards
Tuesdays and Thursdays, after morning report, Beeson left
his office with the residents and students assigned to his
service, walked past the Fitkin Amphitheater and climbed
upstairs to the wards where he consulted for two hours—all
year long. Beeson approached the bedsides of the patients,
who were exposed on all sides and confronted by a crowd of
people they barely knew, and immediately sat down. He had
come to believe, possibly from his practice experience in
Ohio, that standing by a patient’s bedside places the doctor
in a position of dominance that makes many ill people want
to be somewhere else. He wished to place them at ease and
so he reduced the distance between them by sitting unhurriedly, an act that suggested interest in each patient, rather
than the disease being discussed. As the resident presented
the history, physical examination, laboratory and X-ray findings, a task that sometimes took a while, Beeson said nothing. He allowed the younger doctors to discuss the problem
themselves, develop a differential diagnosis, and argue about
what made one possibility more likely than another. If speculations behind the curtains drawn around the bed grew too
33
medical school; this income was not linked to nor influenced
by months spent attending on the wards, number of patients
seen or procedures performed, number of research papers
published nor volume of work done as measured by any other
scale. Patients were admitted through the clinics, emergency
room or privately, and they were taken care of by the same
attending physicians and the same house staff regardless of
their type of insurance—or its lack.
Such administrative issues always impose on the time
of a department chair, and Beeson expected them. What he
did not necessarily expect was the growing line of petitioners
that never seemed to shrink outside his office door.
Beeson still ran the entire department with only
a secretary. Of course, the tasks were far beyond those of a
routine secretarial job. His secretary, Betsy Winters, who
would later have an award, the Betsy Winters House Staff
Award, named in her honor, was responsible not only for
scheduling appointments, phone calls, typing and mimeographing—the general business of running the office—
but also for managing grant applications to the National
Institutes of Health (nih), intern and resident applications and medical student evaluations and monitoring the
queue outside Beeson’s door. Whenever people showed
up, regardless of their rank, Winters found a way to coax
a few more minutes out of the chair’s schedule for them.
outrageous, Beeson gently guided the discussion back
toward reason. Sometimes he said nothing at all, or simply
agreed with the diagnosis and what was being proposed to
manage the illness. Occasionally he differed altogether, as in
the case of a third-year medical student admitted late one
night in 1953.
The student was Sherwin B. Nuland, m.d. ’55, hs ’61,
later a Yale surgeon and gifted writer, who had been brought
to the emergency room with a very high fever and, the admitting resident thought, an enlarged spleen. The temperature
elevation alone wasn’t a great worry, but Nuland was clearly
sick, and a spleen that can be palpated expands the possibilities in several nasty directions. Because they didn’t know
what was the matter with him, the residents did what they
often did then (and now)—they gave him antibiotics and
started to work up the fever. Nuland later noted, “I was evaluated from one end of myself to the other, carrying a diagnosis of either mononucleosis or hepatitis—no one being
sure which. After about three days like this the Professor
came to make rounds, examined me briefly, looked at his
retinue and pronounced, ‘This boy had a strep throat a few
days ago, but he’s fine now. He can be discharged.’ I don’t
suppose this is a major triumph diagnosed by Dr. Beeson,
but what impressed me most was the gentleness with which
he treated his residents when he had shown them to be in
error, and his certainty.”
The tendency toward subspecialization had begun, and
the Department of Medicine was forced to add faculty
members with more focused interests than only general
internal medicine. While recognizing this requirement,
Beeson was reluctant to abandon his lifelong view that
internists should be generalists. But by 1954, this position,
learned from both his father and Soma Weiss, m.d., the
legendary Harvard physician and mentor, was difficult
to defend, and new fellowship-trained faculty members
were hired. With support from Vernon W. Lippard, m.d.
’29, dean of the medical school, Beeson and the Yale
department were now in a position to recruit from the best
talent available.
As the department added more faculty, it also grew
in other dimensions. Space was always an issue (one cardiologist’s lab was in a remodeled coat closet off the Fitkin
Amphitheater), and was relieved only slightly when the
West Haven Veterans Hospital opened. The private Memorial
Unit was constructed, allowing department attending staff
to admit insured private patients and residents an opportunity to care for them, as well as for the nonpaying patients
admitted to the Grace-New Haven Hospital. All of the faculty, with the exception of the dean, were entirely indifferent
to the funding sources for the care of any of these sick people. The faculty and house staff were paid a salary by the
terry dagradi
c u s h i n g / w h i t n e y m e d i c a l / h i sto r i c a l l i b r a r y
A growing faculty and more specialists
o p p o s i t e In 1952, his first year
as chair, Paul Beeson posed with
the faculty in front of the Sterling
Hall of Medicine. Beeson is fifth
from left in the front row. To his
immediate left is nephrologist
John Peters, who made significant
contributions to the study of
renal disease.
a b o v e In May 2003, Paul Beeson
was reunited with nine of his
former residents when he came
to Yale for the unveiling of his
portrait, which hangs in the Fitkin
Amphitheater.
34
Infectious disease, internal medicine and Paul Beeson
A caring mentor
Dedication to the careers of students, residents and faculty is a
labor-intensive activity. The students, who often entered medical school with no idea about what clinical medicine really
involved, were sometimes overwhelmed when they found out.
Patients admitted to teaching centers in the late 1950s were
often so sick they could not be cared for in a community hospital, and the mortality rate was as high as 10 percent on the
Yale medicine wards. These patients were hospitalized for
long periods, and the house staff and students developed relationships with them not available in today’s technology-rich
day-surgery and outpatient environment.
An intern from 1958 remembers his young female
patient with meningitis being treated with the new technique
of injecting intrathecal penicillin, the drug infused into
spinal fluid through a lumbar puncture needle in order to
achieve high concentration at the site of infection. This was
a procedure advocated by Beeson, who recommended that,
even though she was improving, the spinal taps be continued
until the patient was completely without fever. An arithmetical error was made by the nurse preparing the infusion, and
instead of 10,000 units of penicillin, the intern pushed in 1
million. The patient convulsed and died. The intern, who had
been taking care of the young woman since her admission,
also collapsed. Beeson was called by someone still left standing, and immediately came to the ward, gathered both nurse
and intern and took them into an empty room. After the tears
slowed and a little calm had been restored, he explained to
the two young people that errors are certain to be made in the
care of the desperately ill, and that everyone involved in their
care assumes part of the responsibility for what happens on
the wards—the triumph and the loss. By involving himself in
the accident, and reminding them that it was he who chose
the treatment, Beeson comforted the nurse and intern at least
a little, and helped them to know that they were supported.
Next, they told the family exactly what had happened. There
was no lawsuit.
In the first rank of internal medicine
By 1960, the administration of a major department of medicine such as Yale’s had become much more than the chair
and one secretary could manage. A business manager was
added to the staff and took over fiscal responsibility for the
department, as well as management of the growing volumes
of reports that the nih and other funding agencies expected.
Even this increased manpower did little to allow Beeson the
freedom for laboratory research and unhurried individual
meetings with students he had so valued at Emory and during his first years at Yale. He became a clever and capable
administrator, but never the kind of merciless program director consumed by competition for money, faculty and patients.
The Department of Medicine had joined the first rank,
competing with Harvard, Johns Hopkins and Columbia.
A 1964 article about Yale in Newsweek describing the medical
school as “good, if not outstanding,” brought this quietly outraged response from John Bowers, m.d., who had been dean
at two medical schools, member of the Atomic Bomb Casualty
Commission and later president of the Macy Foundation:
“The medical school at Yale has consistently ranked as one of
the top schools in the country, with an excellent faculty and
students. ... Recently a distinguished colleague at a New York
medical school told me the Department of Medicine at Yale
was unquestionably the most outstanding in the country—
and neither he nor I are sons of Old Eli.”
Beeson’s students make their mark
In 1961 Beeson and Robert Petersdorf, his chief resident, published
their landmark paper on Fever in
the journal Medicine. (See sidebar
on opposite page.)
While the department expanded both in depth and scope,
some people left, of course. The vast majority of Beesontrained academics found careers in the best medical schools
in the country; 27 went on to hold major administrative positions at other universities. All of these academic physicians
35
Richard Rapport, m.d., is a neurosurgeon in Seattle.
As head of the Association of
American Medical Colleges,
Robert Petersdorf believed that
medicine had become too
specialized and tried to increase
the number of primary care
physicians entering general internal medicine and family practice.
bachrach
continued to train their own students and house staff in the
image of their teacher, valuing patient care, instruction of
house staff and clinical research above their own advancement.
As the success and size of the department continued
to grow, so did Beeson’s own prestige, both at Yale and nationally. This was not the result of self-promotion, but happened
as a natural function of his unassuming manner and what
Lewis Landsberg, m.d. ’64, hs ’70, and the rest of the house
staff called the “Beeson mystique.”
“What was it, we wondered, that contributed to the
aura of greatness that surrounded this man? When Beeson
walked into a room everybody stood up. His very presence
imbued the Department of Medicine at Yale with an organic
unity that was felt by third-year clerks and full professors
alike. No one wanted to appear unworthy in behavior,
demeanor or medical knowledge in the eyes of Dr. Beeson,”
Landsberg recalled in a letter.
At Yale, Beeson continued to take morning report himself in his office at 8 o’clock, he still attended on the wards
throughout the year and he gave the introductory lecture to
the third-year medical students annually as they began their
clinical training. At this lecture, a gravely ill person was chosen from among the hospitalized patients and brought to the
Fitkin Amphitheater. As students who had studied only basic
sciences, these 24-year-olds about to enter the wards for the
first time had little understanding of the disease being presented. Neither was it their professor’s intent to teach them
details of that specific illness or class of diseases as he carefully and slowly interviewed and then examined the patient
on those fall afternoons. What a comfort it was to these bewildered students when they were then told:
“As your acquaintance with clinical teachers grows, you
will observe that although each of them has special knowledge
and experience in some area of clinical medicine, they make
no pretense of knowing it all. You will also find that clinicians
frequently disagree, and that each of them comes to wrong
conclusions from time to time. ... Biochemists and pharmacologists have ‘hard’ facts to propound. We, on the other hand,
deal with such commodities as pain and nausea. We must
accept any kind of problem. We cannot insist on working with
inbred strains of people, we cannot control the environment
from which they come, we know that their recollection of past
events is faulty and we cannot reduce them to subcellular
fractions to determine what is going on. ... We live, therefore,
in an atmosphere of doubt and uncertainty, and make our
decisions and take our actions on the basis of probabilities. ...
So these are some precepts you must consider: Give each
patient enough of your time. Sit down; listen; ask thoughtful
questions; examine carefully. ... Be appropriately critical of
what you read or hear. ... Follow the example set by William
Osler: ‘Do the kind thing and do it first.’” YM
Alumnus Robert Petersdorf, former
aamc president, dies in Seattle at 80
While this issue of Yale Medicine
was in production, we learned
of the passing of robert g.
petersdorf, m.d. ’52, hs ’58,
former president of the Association of American Medical Colleges
(aamc), as well as chair of the
University of Washington Department of Medicine, dean of the
School of Medicine at the University of California, San Diego, and
president of Brigham and Women’s
Hospital in Boston. It seemed
fitting to remember him on the
same pages as Paul B. Beeson,
m.d., former chair of internal
medicine, who mentored Petersdorf early in his career.
The two met in 1952, when
Beeson had just begun his tenure
as chair and Petersdorf was in his
last year of medical school. In
1996, when Petersdorf accepted
the Kober Medal from the Association of American Physicians, he
remembered what Beeson had
told him that day: “The secret to
success in [academic medicine is]
to get one’s hands dirty in the
laboratory.”
Five years after they met, when
Petersdorf was chief resident,
Beeson asked him to begin working on a paper describing 100
patients who had been ill for more
than three weeks, had episodic
fever of more than 101 degrees and
had remained undiagnosed after
one week in the hospital. This
work was published under both
their names in the journal Medicine
in 1961 as “Fever of Unexplained
Origin,” an article that remains
one of the most frequently cited
papers in medical literature.
Petersdorf went on to lead premier medical centers and departments around the country, as well
as several medical organizations.
He died on September 29 in
Seattle of complications of strokes
at the age of 80. Colleagues
remembered him as a mentor to
young physicians and as one of
the foremost infectious disease
experts in the United States.
As aamc president from 1986
to 1994, Petersdorf sought to
improve the nation’s system of
medical education through efforts
to increase the number of primary-care physicians, strengthen
efforts to enroll underrepresented
minorities, support the role of
teaching hospitals, encourage academic physicians to devote more
time to teaching and advocate for
limits on the demands of residency training. He also succeeded
in improving communication
between medical educators and
Congress, in an era when national
health policies and budgets increasingly affected medical schools
and their teaching hospitals.
36
faculty
Fred Volkmar
Richard Flavell
Jack Elias
Immunobiologist
named to iom
New chairs named
at School of Medicine
richard a. flavell, ph.d. ,
Several new appointments at the
medical school were announced
last summer and fall, with new
leadership in the Department of
Internal Medicine, the Child Study
Center, the Department of Ophthalmology and Visual Science and
the Department of Laboratory
Medicine.
jack a. elias, m.d., the
Waldemar Von Zedtwitz Professor
of Medicine and chief of the
Section of Pulmonary and Critical
Care Medicine, was named chair
of the Department of Internal
Medicine, effective October 1. Elias,
a leading authority on the molecular basis of asthma and other lung
disorders, will lead the school’s
largest department, with 351 fulltime faculty, $83 million in research
funding and $45 million in clinical
activity. Elias, who came to Yale
in 1990, is the author of more than
160 original journal articles and
200 abstracts. He is also a coeditor of the fourth (2007) edition
of the leading textbook in the
field, Fishman’s Pulmonary Diseases
and Disorders. His research focuses
on the cellular and molecular
biology of the lung and processes
related to both injury and repair
of lung tissue. Elias has studied
asthma, emphysema, pulmonary
fibrosis, respiratory syncytial virus
infection and acute lung injury.
Elias succeeds David L. Coleman,
m.d., hs ’80, former interim chair,
who left Yale to become chair of
medicine at Boston University.
fred r. volkmar , m.d.,
a leader in the field of autism
research, was named director of
the Child Study Center and
chief of the Department of Child
Sterling Professor of Immunobiology, and chair of immunobiology
was named to the Institute of
Medicine (iom) in October. The
iom was established by the
National Academy of Sciences and
is recognized as a national resource
for independent, scientifically
informed analysis and recommendations on issues related to human
health. Election to the institute
recognizes people who have made
significant contributions to the
advancement of the medical sciences, health care and public
health and is considered one of
the highest honors in the fields
of medicine and health.
Dean Robert J. Alpern, m.d.,
Ensign Professor of Medicine, said,
“Richard’s research is outstanding,
clearly placing him among the
best immunologists in the world.
This is combined with a talent
for leadership that has allowed
him to cultivate an immunology
program that is unsurpassed anywhere. His wisdom and experience should prove valuable to the
Institute of Medicine.”
Flavell’s research primarily
concerns the molecular basis of
T cell differentiation in the immune system. His research team
has used genomic approaches to
identify the genes that are selectively expressed in T cell lineages, and has used gene targeting,
transgenic mice and retroviral
technology to elucidate the function of these genes and their
target sequences.
Flavell, a Howard Hughes Medical Institute investigator, studies
effector mechanisms of programmed cell death using mice
lacking caspases and investigates the molecular and cellular
basis for autoimmune disease.
James Tsai
Brian Smith
Psychiatry at Yale-New Haven
Hospital for a three-year term,
effective July 1, 2006. The center
is a national and international
leader in the field of children’s mental health. Its programs in early
childhood development, childhood trauma, Tourette syndrome,
obsessive-compulsive disorder,
mental retardation, autism and
other pervasive developmental
disorders are national models.
Volkmar, the Irving B. Harris Professor in the Child Study Center
and professor of child psychiatry,
pediatrics and psychology, came
to Yale as a fellow in 1980 and
joined the medical school faculty
two years later.
An editor of the Handbook
of Autism and Pervasive Developmental Disorders (3rd ed., 2005),
Volkmar was the primary author
of the autism section of the Diagnostic and Statistical Manual of
Mental Disorders, 4th ed. (dsm-iv),
published in 1994. This month he
became editor of the Journal of
Autism and Developmental Disorders, the field’s oldest academic
journal. Volkmar has also made
major contributions to the 2001
monograph, Educating Children
With Autism, written for the Committee on Educational Interventions for Children with Autism of
the National Research Council. He
succeeds Alan E. Kazdin, ph.d., who
had served as director since 2002.
james c. tsai, m.d., m.b.a.,
was named chair of the Department of Ophthalmology and
Visual Science, effective October 1.
Tsai was associate professor of
ophthalmology and director of the
glaucoma division at the Edward
S. Harkness Eye Institute of the
Columbia University College of
Physicians and Surgeons. He succeeds M. Bruce Shields, m.d., who
had served as chair since 1996.
Tsai’s goal for the department
is to make it an internationally
recognized leader in patient care,
vision research and medical education. He plans to recruit clinicians and basic scientists with a
focus on translational studies.
His investigations have concentrated on three areas related to
glaucoma: the search for molecules
with the potential to protect the
optic nerve from damage directly
without lowering intraocular pressure, the evaluation of surgical outcomes in glaucoma patients and
the development of advanced techniques of vision testing.
Tsai is a fellow of the American
Academy of Ophthalmology, the
American College of Surgeons and
the Royal Society of Medicine in
the United Kingdom.
brian r. smith, m.d., has
been named chair of the Department of Laboratory Medicine
and chief of laboratory medicine
at Yale-New Haven Hospital. His
three-year term began on July 1.
Smith has served on the Yale
faculty since 1989. His research
interests in basic and translational
science center on the biology of
the inflammation-coagulation
interface. Since 1997, Smith has
served as vice chair of the department, which is a major center for
research, patient care and teaching in laboratory medicine. The
department has one of the few
National Institutes of Health
research training grants in transfusion medicine and hematopathology. The department
performs nearly 5 million clinical
tests each year.
Smith succeeds Peter I. Jatlow,
m.d., hs ’65, who had headed the
department since 1984.
notes
37
Sven-Eric Jordt
Tarek Fahmy and Erin Lavik
Michelle Bell
Three Yale School of Medicine
researchers investigating schizophrenia, depression and Tourette
syndrome recently received Distinguished Investigator Awards
from the National Alliance for
Research on Schizophrenia and
Depression. The one-year grants
are intended to encourage study
of areas of neuropsychiatric
research that present special
opportunities for discovery.
Angus C. Nairn, ph.d., professor of psychiatry and pharmacology, is studying brain-derived
neurotrophic factor, which has
been implicated in several psychiatric disorders, including
schizophrenia and depression.
Paul J. Lombroso, m.d., the
Elizabeth Mears and House
Jameson Professor of Child Psychiatry in the Child Study
Center, will use an animal model
to investigate the molecular
events associated with Tourette
syndrome, a childhood disorder
characterized by repetitive
movements and vocalizations.
John H. Krystal, m.d., the
Robert L. McNeil Jr. Professor of
Clinical Pharmacology and professor of psychiatry, will use
functional magnetic resonance
imaging to collect pilot data on
20 healthy human subjects to
determine whether certain brain
receptors are related to the cognitive deficits in schizophrenia.
patients. Tarek Fahmy, ph.d., in
collaboration with Joseph Craft,
m.d., professor of medicine and
immunobiology, developed a
platform technology that promises to detect, through magnetic
resonance imaging, cells that
cause autoimmune disease, and
to deliver drugs to those cells.
Two assistant professors have
received Wallace H. Coulter
Foundation Early Career Translational Research Awards in Biomedical Engineering. Erin Lavik,
sc.d., was granted the award
for developing, in collaboration
with scientists at the University
of Iowa, a long-term delivery
system for medications to lower
intraocular pressure in glaucoma
Two Yale environmental scientists were among eight who will
share $3.6 million in grants from
the National Institute of Environmental Health Sciences. The
Outstanding New Environmental
Scientist Award supports earlycareer scientists who make longterm commitments to environmental health research.
Michelle L. Bell, ph.d., assistant professor of environmental
health and of epidemiology and
public health, will study the relationship between outdoor concentrations of ozone and the
incidence of respiratory disease
and death in exposed populations. Sven-Eric Jordt, ph.d., assistant professor of pharmacology,
will study the ways in which airborne pollutants interact with
sensory nerve cells to cause eye,
nose and throat irritation.
Jonathan S. Bogan, m.d., assistant
professor of medicine (endocrinology), has been named one of
five Distinguished Young Scholars
in Medical Research for 2006
by the W. M. Keck Foundation.
Bogan studies the way in which
insulin triggers cells to take up
glucose from the blood.
Myron Genel
Andres Martin
Myron Genel, m.d., professor
emeritus of pediatrics and past
chair of the Association of
American Medical Colleges’
Council of Academic Societies,
was appointed in July to the
Health and Human Services
Secretary’s Advisory Committee
on Human Research Protections.
The 11-member committee
meets three times a year to provide recommendations to the
secretary on the responsible
conduct of research involving
human subjects.
Andres S. Martin, m.d., m.p.h. ’02,
has been named editor of the
Journal of the American Academy
of Child and Adolescent Psychiatry,
effective January 2008. Martin,
an associate professor of child
psychiatry and psychiatry in the
Yale Child Study Center, is also
the medical director of the
Children’s Psychiatric Inpatient
Service at Yale-New Haven
Children’s Hospital.
Annette Molinaro
Barry L. Zaret, m.d., the Robert W.
Berliner Professor of Medicine,
received the Distinguished
Service Award of the American
Society of Nuclear Cardiology at
its annual meeting in Montreal
in September. The award was
based on Zaret’s contributions
to the field of nuclear cardiology
and his 10-year term as the
founding editor in chief of the
Journal of Nuclear Cardiology.
Heping Zhang, ph.d., professor of
biostatistics in the Department
of Epidemiology and Public
Health, was named a fellow of
the Institute of Mathematical
Statistics at their annual meeting in Rio de Janeiro in August.
Hongyu Zhao, ph.d., the Ira V.
Hiscock Associate Professor of
Public Health, has been elected
a fellow of the American Statistical Association, a scientific and
educational society established
to promote excellence in the
application of statistics.
Annette M. Molinaro, ph.d.,
assistant professor of public
health (biostatistics), was
awarded a three-year, $500,000
grant by the National Cancer
Institute in July to develop
statistical methods for searching large sets of genomic, epidemiologic and pathological
data for variables that predict
cancer outcomes.
Marvin Moser, m.d., clinical
professor of medicine, was honored for “Outstanding Contributions to the Advancement and
Promotion of Scientific Research
and Clinical Investigations
Into Blood Pressure Related to
Cardiovascular Health” at the
annual meeting in May of the
American Society of Hypertension in New York.
send faculty news to
Claire M. Bessinger, Yale Medicine,
to claire.bessinger@yale.edu
38
students
the students have much to learn. “But
so much of what you need to be
really good doctors, you already know,”
he said.
Belitsky went on to list the qualities he believes are essential to being
a good doctor. “Becoming a great doctor begins not with what you know,
but who you are. Being someone’s
doctor is about a relationship. That
relationship is built on trust,” he
said. “Being a great doctor begins not
with what you have to say, but your
ability to listen.”
He concluded with what doctors
need to be able to say. “First, ‘I’m
sorry,’ ” he said. “Things go wrong.
Sometimes it’s your fault. Sometimes
it’s nobody’s fault. ... Things go
wrong. Sometimes the most healing
thing that you can do is to acknowledge that by saying ‘I’m sorry.’ ”
Beyond the white coat:
training great doctors
The deputy dean of education discusses
outstanding physicians and what they
must be able to say to their patients.
terry dagradi (3)
In his welcoming speech to 100 members of the Class of 2010 at the White
Coat Ceremony on August 29, Richard
Belitsky, m.d., reminisced about his
own introduction to medical school.
His role models, he said, were the television doctors of his youth. “I wanted
to be smart like Dr. Casey. I wanted
to be compassionate like Dr. Welby.
I wanted to be good-looking like Dr.
Kildare,” he said, provoking laughs
from the audience.
Turning serious, Belitsky, the deputy
dean for education and associate professor of psychiatry, acknowledged that
a b o v e Jonathan Belman, Marie Bewley,
Adriana Blakaj and Gregory Blanton watch as
their classmates don white coats.
t o p r i g h t Deputy Dean Richard Belitsky
welcomes students and parents at a reception
after the ceremony.
b o t t o m r i g h t The Class of 2010 gathers in
the rotunda of the Cushing/Whitney Medical
Library for a group photo.
The other things doctors need to
know how to say include “ ‘I don’t
know,’ ” he said. “Being great doctors
doesn’t mean you have to know everything. You can’t. What is the main
thing you need to know? The limits
of what you know. You can’t just say
‘I don’t know.’ Something else has to
happen. ‘I don’t know … yet. But I
will find out.’ ”
—John Curtis
39
Twenty-nine students in the Physician
Associate Class of 2006 received
their degrees at Commencement in
September, entering a profession that
has grown from small beginnings in
the 1960s to more than 60,000 practitioners with their own national and
specialty organizations. In his address,
Commencement speaker Jerome P.
Kassirer, m.d., noted advances in the
profession but sounded a note of caution for all health care practitioners,
including physician assistants. They
face challenges, he said, over conflicts
of interest, the influence of the pharmaceutical industry and ethical standards not designed for what he called a
“market-driven” health care system.
“What is the antidote to all of these
threats? How do we respond as individuals?” asked Kassirer, editor in chief
emeritus of the New England Journal
of Medicine. “The only antidote I know
for these threats is professionalism.”
He defined professionalism as a
combination of technical competence,
a commitment to self-improvement
and a requirement to use knowledge
and competence in the best interests
of patients. “You alone,” he said, “are
the guardians of your profession.”
Dean Robert J. Alpern, m.d., Ensign
Professor of Medicine, then presented a challenge to the new physician associates.
“I challenge you to strive to be great.
There will be many times in your
careers when you will make a choice,
when you strive to be your best or
just try to get by. I hope you will strive
to be the best,” he said. “You can be
smart. You can be hard-working. But
you have to care for your patients.”
Student awards went to Maura
Brennick, m.m.sc., pa ’06, who
received the Academic Achievement
Award, Anne Flitner, m.m.sc., pa ’06,
who received the Clinical Excellence
Award, and Scott McKay, m.m.sc., pa
’06, who was given the Dean’s Humanitarian Award for his work with the
Student-Run Free Clinic.
The Didactic Instruction Award for
dedication and excellence in the classroom went to Kalpana Gupta, m.d.,
m.p.h., assistant professor of medicine
(infectious diseases). The Clinical
Instructor Award, for a clinical rotation
site that provides exemplary clinical
teaching, was given to two preceptors
in geriatric medicine, Chandrika Kumar,
m.d., of Harborside Healthcare Arden
House in Hamden, Conn., and assistant clinical professor at Yale Geriatric
Services, and Gerard Kerins, m.d., section chief of geriatric medicine at the
Hospital of Saint Raphael. The Jack
Cole Society Award, for significant contributors who support the physician
associate profession, was given to Claire
Hull, pa-c, a former academic coordinator of the program who is now at
Oregon Health & Science University.
—J.C.
j o h n c u rt i s ( 3 )
“You are the guardians of
your profession,” speaker
tells new Physician Associates
t o p Jerome Kassirer, former editor in chief
of the New England Journal of Medicine, urged
graduates to use professionalism to confront
the challenges facing health care practitioners.
m i d d l e Rebecca Pooley, Catherine Rabbitt
and Anne Flitner pose for a photo before the
Commencement ceremony.
b o t t o m Kolby Vaughan, with his daughter,
receives his diploma from Dean Robert Alpern.
40
alumni faces
Juan Lubroth believes avian flu’s real threat
to humans is its ability to disrupt people’s
livelihoods and deny them a source of food.
Avian influenza—
it’s strictly for the birds
Sitting in his Rome office, gazing at
cypress trees and terra cotta rooftops,
Juan Lubroth, d.v.m., m.phil. ’92,
ph.d. ’95, sighs when he hears the
words “avian influenza pandemic”—
not because he foresees the demise of
the human race in a terrifying display
of sickness and death, but because he
believes that such concerns currently
have little merit.
“After over two years of looking at
avian influenza, I do not see an imminent pandemic occurring in humans.
Yes, we have had a little over 100 deaths
in humans attributed to this virus, but
this pales in comparison with deaths
from other pathogens in humans, such
as hiv, tuberculosis and childhood
diarrhea,” Lubroth said during an
interview last spring. And he should
know. As the senior officer and head
of the Emergency Prevention System
(empres) livestock component at the
Food and Agriculture Organization of
the United Nations since 2002, Lubroth
and his team have contained numerous avian influenza outbreaks. From
their analysis of the viral sequence,
they don’t believe we are any closer to
a human pandemic.
“Avian influenza needs to be put
into perspective. Today, I have an epidemic in poultry, and people’s livelihoods and source of protein are at
stake. That is my battle right now—
in poultry,” Lubroth said. To shore up
this form of food security, he and his
allesandro bianchi/reuters
A Yale alumnus who investigates
animal diseases for the UN believes
a human pandemic is unlikely.
team are trying to teach poultry handlers how to improve their hygienic
practices in order to reduce the spread
of avian influenza among chickens
and, in turn, among humans. These
responsibilities fall under Lubroth’s
mandate to track the international
animal trade and ensure that food
products are safe and free from such
infectious agents as those that cause
foot-and-mouth disease, swine fever,
Rift Valley fever and avian influenza,
among others. Lubroth jokes that
he lives in Alitalia—Italy’s national
airline—given his frequent travels
to Thailand, Egypt, Turkey, Vietnam
and China.
As a veterinarian, Lubroth is the
self-described “black sheep” in a
family of architects—his father, grandfather, one of his two brothers, his
sister, an uncle and a cousin are all
architects. Even his only child, 28-yearold Gregorio, is in his third year at
the Yale School of Architecture master’s program. Yet during his childhood
in Madrid, Lubroth found himself
drawn to a different calling. His family’s
large verdant garden, full of animals,
formed a pastoral oasis amidst the
high-rises of the bustling city. Born the
youngest of four children in 1957, it
fell to him to clean up after the family’s
dogs, cats, chickens and ducks. Lubroth
demonstrated an aptitude for caring
for animals, and when he was 12 he
began volunteering at a local veterinary clinic. As he matured, Lubroth
increasingly appreciated the relationship between human health and
animal health, and he felt that investigating that link represented an ideal
strategy for improving the lives of
individuals in developing countries.
To further his education and escape
the political unrest in Spain during
the transition from the dictatorship of
Francisco Franco to democratic rule,
Lubroth accepted a scholarship at
Whitman College in Walla Walla, Wash.,
where he studied biology and played
on the college’s soccer team. At the
University of Georgia he earned a master’s degree in medical microbiology
41
Louis Kirchhoff has spent his career studying
Chagas disease and recently developed an assay
for screening the U.S. blood supply for the
debilitating disease.
A road trip in Latin America
and a lifelong interest in a
debilitating endemic disease
In 1966 a young Harvard graduate
with a B.A. in Romance languages and
literature set out on a three-month
drive through Mexico and Central
America. The part-time interpreter for
the U.S. Department of State never
imagined that his road trip would lead
to a career in medical science.
“The culture was fascinating, the
poverty oppressive, and I got hooked
on Latin America,” recalled Louis V.
Kirchhoff, m.d. ’77, m.p.h. ’77. In
1967, determined to use his fluency
in Spanish and Portuguese to improve
lives, Kirchhoff, the son of a Chicago
insurance agent, became the lone Peace
Corps volunteer in drought-prone
Apodi, a Brazilian town without running water, electricity or paved streets.
Kirchhoff set out to demonstrate
that vegetables could be grown out of
season—a project that would require
irrigation. He rented 2.5 acres of land,
then organized sharecropper families
to build an irrigation system. That led
to year-round crops—and income. By
the early 1970s, Apodi, in the northeastern state of Rio Grande do Norte,
was nicknamed the “Tomato Capital”
of the westernmost region.
Despite the agricultural improvements, Kirchhoff recognized that the
sharecroppers of Apodi had few options.
“They had no access to education, better
jobs or even birth control information,”
he said. Health care consisted of two
pharmacists dispensing informal diagnoses and prescription drugs.
“Everyone had parasites, so I got
a book on them,” recalled Kirchhoff.
That’s when he learned about Chagas
disease, a major cause of morbidity and
death in Latin America that is associated with poverty and a semi-arid climate. The Chagas parasite (Trypanosoma
cruzi) is transmitted when infected
reduviid bugs (also known as triatomine or kissing bugs for their habit of
attacking the face) gorge themselves
on blood drawn from sleeping people
and deposit parasite-laden feces near
the site of the bite wound. The parasites enter the wound when the victim
scratches the bite. Chagas causes
debilitating, sometimes fatal, cardiac
and gastrointestinal manifestations
in 10 to 30 percent of those who have
it, even decades after transmission.
Convinced that infectious diseases
were the biggest health problem in
poor tropical regions, Kirchhoff left
Brazil with a reawakened childhood
career goal. His Russian-born mother
had always urged him to become a
doctor, one of her own criteria for
success in America. He returned to
school and took undergraduate as
well as graduate science and epidemiology courses only to discover—at
26—rampant age discrimination at
most medical schools. Fortunately,
r e x b av o u s e t t
and worked as a wildlife biologist.
While there he met his wife of 24 years,
Adriana, a native of Colombia, at a
concert by the B-52’s. As he puts it,
Lubroth married both Adriana and her
young son, Gregorio. Lubroth stayed
on at the university to earn his veterinary degree, fulfilling a longtime dream.
Since then, Lubroth’s professional
pursuits have led him far and wide:
to New York to study foreign animal
diseases, to Mexico City to prevent
foot-and-mouth disease and to Brazil
for more studies of foot-and-mouth.
Before his appointment to empres,
which is based in Rome, Lubroth
headed the Reagents and Vaccine Section and Diagnostic Services Section
at the Plum Island Animal Disease
Center of the U.S. Department of
Agriculture in New York. During his
travels and many jobs, Lubroth picked
up a second master’s degree along
with a ph.d. from Yale’s Department
of Epidemiology and Public Health,
where he focused his interests in infectious diseases, specifically foot-andmouth disease.
Through it all, Lubroth’s mission
has remained the same: “It is my passion to work with developing countries
to help with their strife by providing
better health, both in animals and in
humans.” Although his nonstop travel
limits his time with his wife and prevents him from weeding through the
stacks of articles and files cluttering
his office, Lubroth is delighted with his
position. “I feel that there is only one
medicine, there is only one health.
Whether it is environmental or wildlife
or livestock, we are dealing with the
same world,” he said.
—Kara A. Nyberg
42
alumni faces
Yale admitted Kirchhoff to its m.d./
m.p.h. program.
In 1976 he found himself back in
Brazil because his thesis advisor,
Alfred Evans, m.d., was studying links
between Epstein-Barr virus (ebv) and
tumors in Brazil. After a lengthy initial
interview, Evans asked, “You don’t
happen to speak Portuguese, do you?”
Kirchhoff spent four months in
São Paulo studying a possible Hodgkin
lymphoma-ebv link. Collecting and
organizing data solidified Kirchhoff’s
love of research and earned him
Yale’s Harold Lamport Biomedical
Research Prize at graduation.
After a residency in internal medicine at Michigan and a four-year fellowship at the National Institutes of Health’s
National Institute of Allergy and
Infectious Diseases, in 1985 he became
an assistant professor at the University
of Iowa College of Medicine and began
studying Chagas genetics and diagnostics. Between 12 and 14 million people
(including about 100,000 residents of
the United States) harbor the Chagas
parasite; about 25,000 die annually,
typically of premature heart disease.
Asymptomatic in 70 to 90 percent of
cases, Chagas is easily transmitted
by blood transfusion. Kirchhoff wanted
to develop an accurate seriodiagnostic
tool to avoid transmission of the parasite by transfusion.
His appointment in 1990 as associate professor of internal medicine,
infectious diseases and epidemiology
at the University of Iowa brought
him nearer to his goal. “Getting tenure
brought more freedom to explore
less traditional avenues of academic
research, in technology transfer and
commercialization,” said Kirchhoff. He
had already developed a radioimmune
precipitation assay, still the gold standard for confirmatory testing, yet
slow and complicated to use. With coinventor Keiko Otsu, he employed
recombinant dna technology to develop
chimeric antigens as the basis of a
test that is accurate and easy to use.
Last year the company he founded
in 1998, Goldfinch Diagnostics, signed
a licensing agreement with Abbott
Laboratories to use the chimeric antigens as the basis of an automated
assay for screening the United States
blood supply for Chagas. The assay
may eventually be marketed in Latin
America as well. And in September
Kirchhoff received a national Tibbetts
Award for the development of the
chimeric antigens.
Settled in Iowa City, Kirchhoff, who
is divorced, continues to attend on
internal medicine and infectious disease services. His children, Alicia,
29, and Aaron, 26, are both artists.
Kirchhoff’s favorite pursuits include
foreign films, National Public Radio
and jogging. (In June, he ran his
sixth marathon—in Argentina.)
“I get an enormous sense of accomplishment thinking about what my
technology may do,” Kirchhoff reflected.
“When the automated assay comes to
market, it will be very satisfying that I
could have an original idea, bang away
at it in my lab for 10 years and finally
be able to more effectively protect transfusion recipients. I will be delighted.”
—Carol Milano
Sharing a home, a family
and science—two alumni try
to make a difference
Jonathan and Bonnie Rothberg share
not only a home and family but also a
passion for probing the mysteries of
the human genome. Together and separately, they attempt both to untangle
genetic differences among individuals
that can affect disease and to develop
novel treatments that target disease at
the genetic and molecular levels.
In 1993, when many scientists were
trying to decipher the human genome,
Jonathan Rothberg, ph.d. ’91, had a
vision: to mine the genome for drug
targets. He founded CuraGen, a company that uses information systems,
automation and robotics to develop
drugs that target specific genes. In the
company’s early years, Jonathan would
bring home sets of newly generated
differential gene expression (dge) profiling data sets and ask his wife, Bonnie
Gould Rothberg, m.d. ’94, m.p.h. ’05,
to apply her medical background to
make sense of the data. By January
1997, midway through her internal
medicine residency at Yale-New Haven
Hospital and with Jordana, the first of
their three children, still an infant, she
decided to place her clinical training
on hold and assume a full-time position designing and analyzing dge data.
So she joined Jonathan at CuraGen,
where she developed a pharmacogenomics program to understand the
mechanisms that underlie differing
responses to drugs. CuraGen developed
five drugs (all in preclinical and clinical
development) for treating cancer, the
adverse effects of chemotherapy, kidney inflammation and type 2 diabetes.
43
j o h n c u rt i s
Bonnie Gould-Rothberg and Jonathan
Rothberg share an interest in science and
medicine, which they advance through
their companies and foundation.
As CuraGen grew, so did the Rothberg family. The birth of their second
child, Noah, in 1999, led Jonathan
to start another company. Noah turned
blue the night he was born and the
doctors had no idea what was wrong.
“I wished I could just read off his
genome,” said Jonathan. “I had a
computer magazine with me and I
thought that since the computer guys
have been able to make things a million times faster and a million times
cheaper by putting them on a chip,
why not the genome?” Noah quickly
turned a healthy pink, but nonetheless
Jonathan created a new company, 454
Life Sciences, to pursue his vision of
sequencing genomes.
454 Life Sciences is also attempting
to reconstruct the genome of Neanderthals, an evolutionary predecessor and
possibly a subspecies of modern Homo
sapiens. “The wonderful thing about
the Neanderthal project is that we may
uncover the molecular basis for the
mind,” Jonathan said. Since the genetic
difference between modern humans
and Neanderthals is only one-twentieth
of 1 percent and the main distinction
between the two species is largely
cognitive, it’s possible that just a handful of genes are involved in human
brain function.
But that’s not the Rothbergs’ only
project. In 2002, Jonathan formed The
Rothberg Institute for Childhood Diseases, a nonprofit organization dedicated to finding a cure for tuberous
sclerosis, a genetic disorder that causes
benign tumors to grow in the brain
and other vital organs throughout the
body, as well as cures for other orphan
diseases of childhood. With three children under the age of five, Bonnie
joined the institute as director of clinical
development. Although her medical
degree served her well, she felt that she
needed formal training in clinical
research design and analysis to conduct
large-scale clinical research. While earning an m.p.h. at Yale, she rediscovered
genomics as a subdiscipline of molecular epidemiology and is now pursuing a
doctorate in chronic disease epidemiology. She is working with David L.
Rimm, m.d., hs ’91, ph.d., associate
professor of pathology, using tissue
microarrays to find proteins that could
serve as prognostic markers for the
speed of growth in melanoma tumors.
Her work has also come full circle: at
CuraGen she participated in the discovery of a drug for melanoma, a disease that she is now studying at Yale,
where the drug is currently being tested.
With 25 U.S. patents, work featured
on the covers of Cell, Science and Nature
and election to the National Academy of
Engineering in 2004, Jonathan has
moved on to his next project, which he
calls the culmination of his life observa-
tions. “If you walk into a lab, it’s very
inefficient,” he said. “So I decided that
instead of just miniaturizing gene
sequencing, why not create a generalpurpose machine very much like a computer but that would move chemicals or
lab components around?” In 2004, he
founded RainDance Technologies to
develop a system for testing, profiling or
sorting samples used in chemistry,
molecular biology and biochemistry on
disposable chips. The company expects
to ship its first machine, which it calls
the Personal Laboratory System, or pls,
in 2007.
Although Jonathan and Bonnie are
both fascinated by science, it wasn’t
their shared academic interests that
brought them together. The two met at
a party in 1993, but only began dating
three months later when Bonnie found
an opening in her on-call schedule.
They were married in 1995. Jonathan
acknowledges that hundreds of dedicated people have helped him turn his
groundbreaking ideas into commercial
successes. But he recognizes that his
most important partnership, in life and
in work, is with Bonnie.
—Jill Max
Familiar Faces
Do you have a colleague who is making
a difference in medicine or public
health or has followed an unusual path
since leaving Yale? We’d like to hear
about alumni of the School of Medicine,
School of Public Health, Physician
Associate Program and the medical
school’s doctoral, fellowship and
residency programs. Drop us a line at
ymm@yale.edu or write to Faces,
Yale Medicine, 300 George Street, Suite
773, New Haven, CT 06511.
44
alumni notes
Aaron Beck
Elizabeth
Blackburn
Three Yale alumni received Lasker
Awards in September for outstanding research in medicine.
For 61 years the Albert Lasker
Medical Research Awards, among
the most coveted in science,
have honored scientists, physicians and public servants who
have made major advances in
the understanding, diagnosis,
prevention, treatment and cure
of many of the great crippling
and killing diseases of the 20th
and 21st centuries.
This year’s recipients include
Aaron T. Beck, m.d. ’46, who on
September 17 received the 2006
Albert Lasker Award for Clinical
Medical Research, “for the
development of cognitive
therapy, which has transformed
the understanding and treatment of many psychiatric conditions, including depression,
suicidal behavior, generalized
anxiety, panic attacks and
eating disorders.”
Beck is university professor
emeritus of psychiatry at the
University of Pennsylvania, where
he joined the faculty in 1954. His
initial research dealt with the
psychoanalytic theories of depression, but he subsequently developed a different theoreticalclinical approach that he called
cognitive therapy. Since 1959
he has directed research into the
psychopathology of depression,
suicide, anxiety disorders, panic
disorders, alcoholism, drug abuse
and personality disorders, as well
as the application of cognitive
therapy to these disorders. His
most recent work has focused on
reducing the number of suicide
attempts among chronic attempters and patients diagnosed with
borderline personality disorder.
The two other Yale alumni
to receive Lasker awards were
colleagues here in the 1970s.
Joseph Gall
Elizabeth H. Blackburn, ph.d.,
fw ’77, sc.d.h. ’91, the Morris
Herzstein Professor of Biology
and Physiology in the Department of Biochemistry and
Biophysics at the University of
California, San Francisco, shared
in the Albert Lasker Award for
Basic Medical Research. She won
the award, along with Carol W.
Greider, ph.d., of Johns Hopkins,
and Jack W. Szostak, ph.d., of
Harvard, for the prediction and
discovery of telomerase, an
enzyme that contains rna and
synthesizes the ends of chromosomes, protecting them and
maintaining the integrity of the
genome. Blackburn began her
research in this area while she
was a postdoctoral fellow at Yale.
Blackburn earned her doctorate from the University of
Cambridge in England in 1975
and did her postdoctoral work
at Yale from 1975 to 1977 in
molecular and cellular biology
in the laboratory of another
2006 Lasker honoree, Joseph G.
Gall, ph.d. ’52.
“As a postdoctoral fellow in
my lab at Yale,” Gall recalled,
“Liz identified the short dna
sequence that defines the
telomeres, or ends of chromosomes. Later when she and her
student, Carol Greider, found
the enzyme (telomerase) that
adds these sequences to
chromosomes, everyone knew
immediately that they had
made a monumental discovery.
Since then, the importance of
their discovery has only grown.”
Among other honors and
awards, Blackburn was named
California Scientist of the Year
in 1999, elected President of
the American Society for Cell
Biology for the year 1998 and
served as a board member of
the Genetics Society of America
(2000-2002). Dr. Blackburn is an
elected fellow of the American
Academy of Arts and Sciences
(1991), the Royal Society of
London (1992), the American
Academy of Microbiology (1993)
and the American Association
for the Advancement of Science
(2000). She was elected Foreign
Associate of the National Academy of Sciences in 1993, and was
elected as a member of the
Institute of Medicine in 2000.
Gall received the Albert Lasker
Award for Special Achievement
in Medical Science, “for a distinguished 57-year career—as a
founder of modern cell biology
and the field of chromosome
structure and function; bold
experimentalist; inventor of in
situ hybridization; and early
champion of women in science.”
Gall, now at the Carnegie
Institution (Department of
Embryology at Baltimore), ranks
among the most distinguished
cell biologists in the history of
the discipline.
Among Gall’s awards are the
2004 Society for Developmental
Biology Lifetime Achievement
Award and the 1996 American
Association for the Advancement of Science Mentor Award
for Lifetime Achievement. In
1988 he received the Wilbur
Lucius Cross Medal, the highest
honor bestowed by the Yale
Graduate School on exceptionally distinguished alumni.
1950s
Eiji Yanagisawa, m.d., hs ’59, clini-
cal professor of otolaryngology,
received the Presidential Citation
from the American Laryngological, Rhinological and Otological
Society at its 109th annual meeting in Chicago in May. The award
was given in recognition of his
contributions to otolaryngology
and head and neck surgery.
1970s
Deborah Rose, m.p.h. ’77, ph.d. ’89,
has been selected by the Association of Yale Alumni (aya) to
receive the Yale Medal, the highest award presented by the aya
and conferred in recognition of
outstanding service to the university. Since its inception in
1952, the Yale Medal has been
presented to 257 individuals,
all of whom not only showed
extraordinary devotion to the
ideals of the university, but also
demonstrated their support
of Yale through extensive and
exemplary voluntary service on
behalf of Yale as a whole or one
of its many schools, institutes or
programs. Rose has served her
class as secretary, class council
member and reunion chair. Her
dedication extends beyond
her class to many areas of the
university and the surrounding
community, including the Sterling Memorial Library, Jonathan
Edwards College and the new
Rose Center that houses both
the Yale Police Department and
the Dixwell Community Center.
45
Kate Lally and Antony Chu
Alejandro Necochea and
Lauren Smith
Vicki Shi and Edward Poon
She initiated computerization of
the branch libraries of the New
Haven Free Public Library. A
longtime supporter of Yale’s initiatives to help revitalize the city
of New Haven, Rose has worked
since her earliest days at Yale
with community outreach
programs through Dwight Hall,
the Yale-affiliated student-run
public service organization.
Conn., and continues her research
on early modern health care. She
and her husband, Remo Fabbri Jr.,
m.d. ’64, look forward to hearing
from any alumni visitors when
in town.
Joanne N. Quinones, m.d. ’98,
Bryon P. Wenrich, pa ’98, and big
Robert E. Steele, m.p.h. ’71, ph.d.
’75, president of the Association
of Yale Alumni in Public Health
(ayaph), has received the 2006
Nathan Hale Award for his
efforts in establishing a Nathan
Hale Scholarship in 2006, which
is being named the Association
of Yale Alumni in Public Health
Board Scholarship. The scholarship will be awarded to a student in the Department of
Epidemiology and Public Health
(eph). Steele has made fundraising one of the top priorities
of the ayaph board. During his
presidency Steele has ensured
that the eph Alumni Fund
reaches its goal by writing
letters, calling alumni, negotiating with major donors and
contributing his own funds.
1980s
Christiane Nockels Fabbri, pa-c
’84, received a doctorate in history from the Graduate School
of Arts and Sciences in May
2006. Her dissertation, a survey
of medieval and early modern
treatises on the plague, analyzes
continuity and change in plague
medicine from 1348 to 1599.
Fabbri was associate director of
the Yale Physician Associate
Program from 1991 to 2000, and
was voted Distinguished Alumna
in 2004. She currently practices
family medicine in West Haven,
Justin O. Schechter, m.d., hs ’85,
assistant clinical professor of
psychiatry, has been appointed
by Gov. M. Jodi Rell to serve on
the Psychiatric Security Review
Board (psrb) in the state of
Connecticut. The psrb is a state
agency to which the Superior
Court commits persons who are
found not guilty of a crime by
reason of mental disease or
mental defect. The psrb reviews
the status of acquittees through
an administrative hearing
process and orders the level of
supervision and treatment for
the acquittee considered necessary to protect the public.
Schechter, who has a special
interest in forensic psychiatry, has
also been appointed an associate fellow of Silliman College.
sister Elena Sofia proudly
announce the arrival of William
Carlos Wenrich-Quinones, born
December 29, 2005. Quinones
is an attending physician in
maternal-fetal medicine at Lehigh
Valley Hospital in Allentown, Pa.,
and Wenrich is a cardiothoracic
surgery physician assistant at
Lankenau Hospital in Wynnewood, Pa. Yale classmates can
reach the Wenrich-Quinones
clan at jqwenrich@yahoo.com.
2000s
Kate M. Lally, m.d. ’02, and Antony
F. Chu, m.d. ’02, were married in
July in Bedford, N.H. Lally is an
internist at a group practice in
Radnor, Pa. Chu is a cardiology
fellow at the University of
Pennsylvania. Both were Howard
Hughes Medical Institute fellows. Lally studied melanoma at
the National Institutes of Health
and Chu did work in vascular
biology at Yale.
hometown, when he was on
leave from medical school to
study tuberculosis in shantytowns and she was there on a
Fulbright scholarship, studying
microfinance, the provision
of small loans to women entrepreneurs.
Rahul Rajkumar, j.d. ’06, m.d.
’06, was married in May to
Usha-Kiran Ghia, j.d., in Cincinnati. Rajkumar recently began an
internship in internal medicine
at Brigham and Women’s Hospital in Boston. Ghia began clerking in October for a Federal
District Court judge in Boston.
Vicki Shi, m.p.h. ’00, manager in
strategic marketing for Johnson
& Johnson’s pharmaceuticals
division in New Jersey, was married in August to Edward Poon,
m.d., a radiologist also based in
New Jersey. Fellow eph grads
who attended included Sobin
Chang, m.p.h. ’97, Nicole Durbin,
m.p.h. ’00, Scott Durbin, m.p.h.
’99, and Greg Kruse, m.p.h. ’01.
1990s
Stephanie M. Marticello, m.p.h.
Jonathan N. Grauer, m.d. ’97, was
married in August to Jane S.
Merkel, ph.d. ’00, in New Haven.
Grauer is a director of the orthopaedic spine service and an
assistant professor of orthopaedics and rehabilitation at the
School of Medicine. Merkel is
director of chemical genomics at
the Center for Genomics and
Proteomics at Yale.
’04, was married in June to
Christopher M. Poulin in Thomaston, Conn. Marticello works as
an epidemiologist with the state
Department of Public Health.
send alumni news to
Alejandro J. Necochea, m.d. ’04,
visit us on the web
was married on July 1 to Lauren
B. Smith, m.p.a., in Philadelphia.
Necochea is a third-year resident in internal medicine at the
Hospital of the University of
Pennsylvania. Smith is a policy
analyst fellow with joint
appointments at the Robert
Wood Johnson Foundation in
Princeton, N.J., and the Center
for Health and Wellbeing at
Princeton University. The two
met in Lima, Peru, Necochea’s
46
in memoriam
John L. Binder, m.p.h. ’85, a
colonel in the U.S. Air Force, died
on September 7 following a
battle with cancer. He was 49.
A resident of Yorktown, Va.,
Binder served 21 years in the Air
Force, most recently as chief of
the Expeditionary Medical Operations Division, Headquarters Air
Combat Command at Langley
Air Force Base in Hampton, Va.
His duties included directing
functions for medical readiness
operations, providing medical
forces and support to planners
throughout the world. His career
took him all over the world and
he served in Korea, Turkey,
Germany, Hawaii and the continental United States. As an
executive officer at Ramstein Air
Base in Germany, Binder was
instrumental in the November
1991 repatriation of Terry Waite
and Thomas Sutherland, who
had been hostages in Beirut in
the late 1980s and early 1990s.
Colonel Binder recently received
the Legion of Merit Medal signifying meritorious and distinguished service.
Charles R. Cavanagh Jr., m.d. ’47,
died on May 6 In Spokane, Wash.
He was 83. Cavanagh served in
the Navy Reserve while in medical school and in the Air Force,
where he was chief of surgery at
Fairchild Air Force Base in
Washington. After his military
service he formed the Spokane
Surgical Group.
William L. Donegan, m.d. ’59, died
on July 17. He was 73. An academic and athletic standout in
high school in Florida, Donegan
earned scholarships to Exeter
Academy, Yale University and
the School of Medicine. He completed his residency at Barnes
Hospital-Washington University
School of Medicine in St. Louis.
At Ellis Fischel State Cancer
Hospital in Columbia, Mo., he
developed his expertise in surgical oncology. In 1974 he joined
the faculty of the Medical
College of Wisconsin, where he
spent the next 29 years.
Richard K. Friedlander, m.d. ’47,
died on June 3 in Geyersville,
Calif. He was 82. After serving as
house physician at the American
Hospital in Paris, Friedlander
went to San Francisco to train as
a psychiatrist at the Langley
Porter Neuropsychiatric Institute
at the University of California,
San Francisco (ucsf). He also
worked in emergency psychiatric
services at San Francisco General
Hospital and the student health
service at ucsf. He retired in 1983.
Howard H. “Howdy” Groskloss,
m.d. ’35, died on July 15 at vna
Hospice House in Vero Beach,
Fla. He was 100. While at the
School of Medicine, Groskloss
also played professional baseball
for the Pittsburgh Pirates, from
1930 to 1932. He practiced
gynecology for more than 25
years and during World War II he
was a Navy flight surgeon.
Terry L. Hatmaker, m.p.h. ’74, died
on July 30 in High Point, N.C.
He was 59. Born in LaFollette,
Tenn., Hatmaker grew up in
Oregon. He worked at the Center
for Life Cycle Analysis (lca) at
Oak Ridge National Laboratory
in Tennessee, helping to develop
an lca system for the U.S.
Department of Energy (doe) to
assist in making decisions about
decontamination at various doe
sites. The lca system is intended
to minimize risks to human
health and added insults to the
environment.
Jay G. Hayden II, m.d. ’66, died on
May 20 after a struggle with
pulmonary fibrosis. He was 66.
An anesthesiologist, Hayden
served in the U.S. Air Force at
Andrews Air Force Base, then
worked at the Lahey Clinic in
Massachusetts. In 1982 he
moved to Maine and worked
at the Maine Medical Center’s
Spectrum Medical Group.
Gueh-Djen (Edith) Hsiung, ph.d.,
an internationally recognized
virologist and professor emeritus in the Department of
Laboratory Medicine, died of
cancer on August 20, at Connecticut Hospice in Branford.
She was 87. Hsiung was a pioneer in the field of diagnostic
virology and known for the
techniques she invented to
detect and characterize viruses.
She authored a landmark textbook, established laboratories
and trained generations of new
professionals in the field, even
into her early 80s. She was also
known for her development
of animal models to study the
pathogenesis and treatment of
viral infections. Hsiung was born
in Hupei, China, and graduated
with a degree in biology from
Ginling College in Chengdu in
1942. During World War II she
tested bacterial and viral vaccines for use in animals at the
Ministry of Public Health in
Lanzhou. After the war, she
came to the United States and
obtained her doctorate in microbiology from Michigan State
University in 1951. She applied
for admission to medical school
at Yale but was told she was too
old. Instead she was offered a
postdoctoral fellowship in 1953,
working under Joseph L.
Melnick, ph.d. ’39, on poliovirus
and related enteroviruses. She
joined the faculty the next year
and, aside from a two-year
sojourn at New York University,
spent her entire professional
career at Yale.
John K. Joe, m.d., hs ’00, assistant
professor of otolaryngology, died
suddenly on August 8. He was 36.
Joe came to Yale in 1995 as an
intern in the Department of
Surgery and completed his residency in otolaryngology in 2000.
After a fellowship at Memorial
Sloan-Kettering Cancer Center
and an assistant professorship at
the Medical University of South
Carolina, Joe returned to Yale in
2003 to join the faculty of the
Section of Otolaryngology in the
Department of Surgery. He rapidly
established himself as a premier
head and neck surgeon and developed one of the largest head
and neck surgical oncology practices on the East Coast. He specialized in treating patients with
advanced and complex cancers
and offered the highest level of
technical and compassionate care.
Frederick F. Krauskopf, m.d. ’44,
died on August 7 in Florida.
He was 87. Born in Germany,
Krauskopf came to the United
States when he was 5. After a
residency at Jackson Memorial
Hospital in Miami, he served in
a U.S. Medical Corps m.a.s.h.
unit in Korea. He subsequently
served as chief of surgery at
Fort McClellan, Ala., and at the
Walter Reed Army Hospital in
Washington. He also served
as chief of surgery and deputy
commander of the Medical
Center of the European Theater
in Landstuhl, Germany. After
serving as chief of surgery at
Martin Army Hospital at Fort
Benning, he retired to private
practice in Stuart, Fla.
47
Victor A. Machcinski Sr., m.d. ’47,
died of cancer in West Chatham,
Mass., on May 11. He was 82.
Machcinski interned at GraceNew Haven Community Hospital and completed a surgical
residency at New Britain Hospital. He served in Korea with the
U.S. Army Medical Corps and
was awarded the Bronze Star. A
fellow of the American College
of Surgeons, he practiced at
Danbury Hospital for 31 years.
Ralph G. Maurer, m.d. ’67, died
on May 12. He was 62. Maurer
served as a major in the Medical
Corps, U.S. Air Force Reserve, at
the School of Aerospace Medicine in San Antonio. For the last
26 years he was on the faculty
at the University of Florida
College of Medicine, where he
was an associate professor of
psychiatry and director of the
Center for Autism and Related
Disabilities.
Iwao M. Moriyama, m.p.h. ’34,
ph.d. ’37, died on June 10 in
Cheverly, Md., of complications
from injuries sustained in a fall.
He was 97. In 1940 Moriyama
joined the U.S. Public Health Service in Washington, where he
worked for more than 30 years.
He served on the National Committee on Vital and Health
Statistics and the World Health
Organization’s Expert Panel on
Health Statistics. During his
retirement he spent three years
studying health risks from radiation exposure in Hiroshima,
Japan.
Richard M. Peters, m.d. ’45, died
of metastatic melanoma on
September 1 at his home in Palo
Alto, Calif. He was 84. Peters was
born in New Haven, the son of
John P. Peters, m.d., a distin-
guished professor of medicine at
the School of Medicine. After
graduating, Peters served as a
medical officer in the Army, and
in 1952 he became assistant professor of surgery and head of
cardiothoracic surgery at the
University of North Carolina
at Chapel Hill. In 1954 he was
instrumental in opening the
first intensive care unit in the
United States for postsurgical
patients at North Carolina
Memorial Hospital. Eight months
later it became the first desegregated ward in the hospital, a
precedent that led to the eventual desegregation of the entire
hospital. In 1963 Peters’ research
on pulmonary mechanics led
him to recognize the need to
use computer and physiology
methodologies to collect and
analyze pulmonary mechanics
and work done on the lungs. He
also established a postgraduate
curriculum in bioengineering,
one of the first of its kind in the
country. In 1961 he was elected
to the Chapel Hill School Board
and was instrumental in desegregating the city’s public schools,
making it the first totally desegregated school system in the
South. In 1969, Peters became
head of the division of cardiothoracic surgery and bioengineering at the new University of
California, San Diego, School of
Medicine. Throughout his career,
Peters was very interested in the
teaching of medical students,
residents and fellows. He served
as head of the examination
committee for the American
Board of Thoracic Surgery and
developed the automated system for construction of the written examination. He published
250 articles and a book on respiratory mechanics; was senior
editor of five textbooks, includ-
ing a comprehensive text on cardiothoracic surgery published in
China; and was a contributing
author to books on pulmonary
mechanics, fluid management
and thoracic surgery.
Hannah C. Russell, r.n., m.p.h.
’60, died on September 13 in
Avon, Conn. She was 95. Russell
worked as an operating room
nurse at Columbia Presbyterian
Hospital in New York. She also
worked at the Visiting Nurse
Association in New Haven. She
was an assistant professor of
nursing at the University of
Bridgeport and a Red Cross
instructor during World War II.
She was on the Planning and
Zoning Commission in Orange,
Conn., and served as a state representative in the Connecticut
legislature.
Bradford Simmons, m.d. ’39, died
on July 13 at Marin General
Hospital in California. He was
94. An athlete, Simmons played
football, rowed crew and was a
heavyweight boxer. During
World War II he was a Navy
flight surgeon, and after the war
he practiced at Southern Pacific
Hospital, Marin General Hospital
and San Quentin Prison. After
retiring he served on the ship
Hope in Brazil, at a Quaker hospital in Kenya, at a hospital in
Samoa and on the Navajo Indian
Reservation at Shiprock, N.M.
Charles A. Slanetz Jr., m.d. ’57,
died on June 12 in Locust Valley,
N.Y. For 41 years Slanetz practiced general surgery in Glen
Cove, N.Y. He also had staff positions at North Shore Hospital
and at the University Hospital at
Stony Brook, N.Y. His research on
colon cancer was published in
several journals.
Lester J. Wallman, m.d. ’38, died
on July 23 in Burlington, Vt.,
where he lived and practiced
medicine since 1947. Wallman
was born in New York City and
received his undergraduate and
medical degrees from Yale. He
trained in pathology in Sweden,
in general surgery in Delaware
and in neurology and neurosurgery in Connecticut. After leaving the U.S. Army in 1946 as a
captain, Wallman completed his
neurosurgery training in
Vermont. He joined the faculty
of the University of Vermont in
1948. Wallman was named
professor emeritus in 1992. He
wrote a chapter in the university’s bicentennial history and
established the Beaumont
Medical History Lecture Series.
He also served as chair of the
Vermont State Board of Health
and on many civic boards,
including that of the Vermont
chapter of the American Red
Cross.
Paul B. Beeson, m.d., and Robert
G. Petersdorf, m.d. ’52, hs ’58, are
remembered on pages 30–35.
send obituary notices to
archives 50 and 25 years ago
follow-up
j o h n c u rt i s
48
Ovarian cancer screening to reach patients
Physicians refer to epithelial ovarian cancer as “the silent
killer.” With few early symptoms, the disease often goes undetected until it has spread to other parts of the body and it’s
too late for curative treatment. It ranks as the deadliest of all
gynecological cancers, claiming approximately three of every
four women in the United States diagnosed with the disease.
Now a scientific team led by Gil Mor, m.d., ph.d., associate professor of obstetrics, gynecology and reproductive sciences, has
found a way to detect the disease in its earliest stages, and
has teamed with biopharmaceutical companies to transfer
this technology from the bench to the bedside.
In May 2005, Mor and colleagues, in an article in the
Proceedings of the National Academy of Sciences, showed that
abnormal concentrations of four cancer-related proteins—
leptin, prolactin, osteopontin and insulin-like growth factor
II—in blood samples could indicate the presence of epithelial
ovarian cancer with 95 percent accuracy and 95 percent specificity. [See “Biomarkers Warn of a ‘Silent Killer’,” Autumn 2005.]
Since then they have added two other protein markers
and the accuracy rate has risen to 98 percent and the specificity rate to greater than 99.6 percent. This means that only
20 of every 1,000 women screened will be mistakenly diagnosed as being cancer-free, while only four of every 1,000
screenings will yield false positives.
Now the research team is pursuing partnerships with
biotech companies throughout the world to develop this technology commercially. Yale recently signed a licensing agreement with SurExam Life Science & Technology Co., a Chinese
company founded in part by scientists trained at Yale, and
negotiations are under way to license the technology to a new
diagnostic company in Israel.
Mor predicts that the test will be available in the
United States early this year, following the completion of a
pivotal Phase II trial being conducted by the National Cancer
Institute in partnership with Laboratory Corporation of
America. He hopes that his blood screen will be routinely used
to detect epithelial ovarian cancer. “At the beginning, we
thought this test may be appropriate only for women at high
risk, but we now see this test as becoming a more routine
diagnostic for screening,” he said.
—Kara A. Nyberg
Yale Receives Top Ford
Foundation Grant
—Alumni Bulletin
May 1957
“A record-setting grant of
$3,600,000 to the Yale School of
Medicine from the Ford Foundation was announced in March as
part of the Foundation’s program
to strengthen instruction in the
nation’s private medical schools.
The Ford Foundation is making
awards totaling $90,000,000 to
the nation’s 45 private medical
schools. The money is to be held
as invested endowment for at
least 10 years. The income from
endowment may be used for
instructional purposes but not for
construction or research needs.
After the 10-year period, Yale and
the other recipient medical
schools are free to use the principal sum as well as endowment
income. ...
“Dean [Vernon W.] Lippard, in
commenting on the Ford Foundation award, said: ‘This is the
largest gift ever received by the
Yale School of Medicine. Its importance is not related to its size
alone but rather to the fact that it
is designated for unrestricted
endowment. The income will be
used in support of the basic operation of the school and improvement of its educational program.
Yale will be forever grateful to the
Ford Foundation.’ ”
“The Move” Into New Patient
Care Facility
—Yale Medicine
Spring /Summer 1982
“The first patients moved into the
Yale-New Haven Hospital’s new
seven-story patient-care facility on
April 21, culminating nearly 20
years of planning and three years
of construction. The enormous
task of moving patients, staff and
equipment from the outmoded
New Haven Unit and parts of the
Memorial Unit was launched amid
balloons, flowers and a spirit of
festivity in the pristine, attractive
new facility. …
“The $73 million project replaces
outdated facilities located across
the street in the New Haven Unit
with a modern, comfortable and
integrated patient-care area. The
project also includes renovation of
the childbirth facilities in the
Memorial Unit.
“The building has enabled the
Hospital to consolidate the departments of radiology, pediatrics,
the operating rooms, admitting
and discharge offices and the
cafeterias. The new emergency
room located on the first floor
has doubled in size. Patient rooms
on floors five through seven have
been designed with privacy and
comfort in mind.”
end note
Since Kyeen Mesesan, an m.d./ph.d. candidate at the School of
Medicine, began her dissertation project in South Africa in 2003,
she has received accolades and invitations to present at conferences. But nothing was quite like the 16th International aids
Conference in Toronto in August, where she presented a paper on
adult male circumcision programs and hiv.
“I had an idea it would be a bit contentious,” said Mesesan.
“We’re talking about a surgery to prevent hiv.” Indeed, activists at
the conference raised pointed questions about genital mutilation,
race and gender. But the idea has gained currency as the notion of
a single magic bullet against aids gives way to multiple measures
to prevent hiv infection.
Circumcision was not originally part of Mesesan’s research—
she was exploring a hypothetical question. “What does a country
like South Africa do 10 years from now if a partially effective
vaccine comes out—say 30 percent effective—and they have to
decide whether they’re going to use it on their population?” she
asked. Mesesan put this question in the context of other risk
factors, such as sexual behavior and condom use. “Although in
most scenarios such a low-efficacy vaccine would be beneficial, in
some scenarios you could actually make the epidemic worse.”
Her research took a detour in July 2005 when, in a study in
South Africa, French researchers linked male circumcision to a
61 percent reduction in female-to-male transmission of the virus.
Mesesan took that number and, applying statistical modeling
techniques, estimated that in the township of Soweto, a five-year
prevention program that boosted the current 35 percent circumcision rate by 10 percent would prevent 53,000 infections.
“While even a low-efficacy hiv vaccine may be decades
away, circumcision is effective and the technology is available
immediately,” Mesesan stated. In December trials in Kenya
and Uganda showed that circumcision reduced the risk of aids
from heterosexual sex by half.
—John Curtis
j o h n c u rt i s
“A S U R G E RY TO P R E V E N T H I V ”
Kyeen Mesesan used statistical modeling to
determine how many new hiv infections adult
male circumcision could prevent in a township
in South Africa.
yale medicine 300 george street, suite 773, new haven ct 06511
Save the Date! June 1 – 2, 2007
winter 2007
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Permit No. 696
Yale School of Medicine
Alumni Reunion Weekend
Reminisce with classmates.
See what’s new.
Stroll down Cedar Street.
Reconnect.
Classes ending in 2 and 7 will be holding special celebrations this year.
All alumni are welcome to attend Alumni Reunion Weekend.
To learn more about this year's program, please call (203) 436-8551
or visit ourwebsite at http://info.med.yale.edu/ayam

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